{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:41:23Z","timestamp":1790239283639,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 CA097132"],"award-info":[{"award-number":["P01 CA097132"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003286","name":"Kuwait Foundation for the Advancement of Sciences","doi-asserted-by":"publisher","award":["RA AM 2016- 007"],"award-info":[{"award-number":["RA AM 2016- 007"]}],"id":[{"id":"10.13039\/501100003286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ceramide kinase (CERK) phosphorylates ceramide to produce ceramide-1-phosphate (C1P), which is involved in the development of metabolic inflammation. TNF-\u03b1 modulates inflammatory responses in monocytes associated with various inflammatory disorders; however, the underlying mechanisms remain not fully understood. Here, we investigated the role of CERK in TNF-\u03b1-induced inflammatory responses in monocytes. Our results show that disruption of CERK activity in monocytes, either by chemical inhibitor NVP-231 or by small interfering RNA (siRNA), results in the defective expression of inflammatory markers including CD11c, CD11b and HLA-DR in response to TNF-\u03b1. Our data show that TNF-\u03b1 upregulates ceramide phosphorylation. Inhibition of CERK in monocytes significantly reduced the secretion of IL-1\u03b2 and MCP-1. Similar results were observed in CERK-downregulated cells. TNF-\u03b1-induced phosphorylation of JNK, p38 and NF-\u03baB was reduced by inhibition of CERK. Additionally, NF-\u03baB\/AP-1 activity was suppressed by the inhibition of CERK. Clinically, obese individuals had higher levels of CERK expression in PBMCs compared to lean individuals, which correlated with their TNF-\u03b1 levels. Taken together, these results suggest that CERK plays a key role in regulating inflammatory responses in human monocytes during TNF-\u03b1 stimulation. CERK may be a relevant target for developing novel therapies for chronic inflammatory diseases.<\/jats:p>","DOI":"10.1038\/s41598-021-87795-7","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T06:18:05Z","timestamp":1618467485000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Ceramide kinase regulates TNF-\u03b1-induced immune responses in human monocytic cells"],"prefix":"10.1038","volume":"11","author":[{"given":"Fatema","family":"Al-Rashed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunair","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley J.","family":"Snider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reeby","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihab","family":"Kochumon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motasem","family":"Melhem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sardar","family":"Sindhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina M.","family":"Obeid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf A.","family":"Hannun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasheed","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"87795_CR1","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.bbalip.2013.02.001","volume":"1831","author":"A Gomez-Mu\u00f1oz","year":"2013","unstructured":"Gomez-Mu\u00f1oz, A. et al. New insights on the role of ceramide 1-phosphate in inflammation. Biochim. et Biophys. Acta Mol. Cell Biol. Lipids 1831, 1060\u20131066. https:\/\/doi.org\/10.1016\/j.bbalip.2013.02.001 (2013).","journal-title":"Biochim. et Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"87795_CR2","doi-asserted-by":"crossref","unstructured":"Bajjalieh, S. M., Martin, T. F. & Floor, E. Synaptic vesicle ceramide kinase. A calcium-stimulated lipid kinase that co-purifies with brain synaptic vesicles. J. Biol. Chem. 264, 14354\u201314360 (1989).","DOI":"10.1016\/S0021-9258(18)71685-2"},{"key":"87795_CR3","doi-asserted-by":"publisher","first-page":"17570","DOI":"10.1074\/jbc.M312885200","volume":"279","author":"S Mitsutake","year":"2004","unstructured":"Mitsutake, S. et al. Ceramide kinase is a mediator of calcium-dependent degranulation in mast cells. J. Biol. Chem. 279, 17570\u201317577. https:\/\/doi.org\/10.1074\/jbc.M312885200 (2004).","journal-title":"J. Biol. Chem."},{"key":"87795_CR4","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.imlet.2004.09.001","volume":"96","author":"T Baumruker","year":"2005","unstructured":"Baumruker, T., Bornancin, F. & Billich, A. The role of sphingosine and ceramide kinases in inflammatory responses. Immunol. Lett. 96, 175\u2013185. https:\/\/doi.org\/10.1016\/j.imlet.2004.09.001 (2005).","journal-title":"Immunol. Lett."},{"key":"87795_CR5","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.bbalip.2016.02.007","volume":"1861","author":"N Presa","year":"2016","unstructured":"Presa, N. et al. Regulation of cell migration and inflammation by ceramide 1-phosphate. Biochim. Biophys. Acta 1861, 402. https:\/\/doi.org\/10.1016\/j.bbalip.2016.02.007 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"87795_CR6","doi-asserted-by":"publisher","first-page":"E1213","DOI":"10.1152\/ajpendo.00480.2012","volume":"304","author":"L Arana","year":"2013","unstructured":"Arana, L. et al. Ceramide 1-phosphate induces macrophage chemoattractant protein-1 release: Involvement in ceramide 1-phosphate-stimulated cell migration. Am. J. Physiol. Endocrinol. Metab. 304, E1213\u2013E1226. https:\/\/doi.org\/10.1152\/ajpendo.00480.2012 (2013).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"87795_CR7","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.febslet.2012.03.032","volume":"586","author":"S Mitsutake","year":"2012","unstructured":"Mitsutake, S. et al. Ceramide kinase deficiency improves diet-induced obesity and insulin resistance. FEBS Lett. 586, 1300\u20131305. https:\/\/doi.org\/10.1016\/j.febslet.2012.03.032 (2012).","journal-title":"FEBS Lett."},{"key":"87795_CR8","doi-asserted-by":"publisher","first-page":"42665","DOI":"10.1038\/srep42665","volume":"7","author":"K Wouters","year":"2017","unstructured":"Wouters, K. et al. Circulating classical monocytes are associated with CD11c. Sci. Rep. 7, 42665. https:\/\/doi.org\/10.1038\/srep42665 (2017).","journal-title":"Sci. Rep."},{"key":"87795_CR9","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.cmet.2013.02.009","volume":"17","author":"T Deng","year":"2013","unstructured":"Deng, T. et al. Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation. Cell Metab. 17, 411\u2013422. https:\/\/doi.org\/10.1016\/j.cmet.2013.02.009 (2013).","journal-title":"Cell Metab."},{"key":"87795_CR10","doi-asserted-by":"publisher","first-page":"2927","DOI":"10.4049\/jimmunol.1600476","volume":"198","author":"J Braune","year":"2017","unstructured":"Braune, J. et al. IL-6 regulates M2 polarization and local proliferation of adipose tissue macrophages in obesity. J. Immunol. 198, 2927\u20132934. https:\/\/doi.org\/10.4049\/jimmunol.1600476 (2017).","journal-title":"J. Immunol."},{"key":"87795_CR11","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.4049\/jimmunol.1701552","volume":"200","author":"R Ahmad","year":"2018","unstructured":"Ahmad, R. et al. The synergy between palmitate and TNF-\u03b1 for CCL2 production is dependent on the TRIF\/IRF3 pathway: Implications for metabolic inflammation. J. Immunol. 200, 3599\u20133611. https:\/\/doi.org\/10.4049\/jimmunol.1701552 (2018).","journal-title":"J. Immunol."},{"key":"87795_CR12","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.1182\/blood-2008-02-137711","volume":"112","author":"R Ahmad","year":"2008","unstructured":"Ahmad, R., El Bassam, S., Cordeiro, P. & Menezes, J. Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1. Blood 112, 2360\u20132368. https:\/\/doi.org\/10.1182\/blood-2008-02-137711 (2008).","journal-title":"Blood"},{"key":"87795_CR13","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/978-1-60761-322-0_22","volume":"579","author":"J Bielawski","year":"2009","unstructured":"Bielawski, J. et al. Comprehensive quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry. Methods Mol. Biol. 579, 443\u2013467 (2009).","journal-title":"Methods Mol. Biol."},{"key":"87795_CR14","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1139\/o59-099","volume":"37","author":"EG Bligh","year":"1959","unstructured":"Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911\u2013917. https:\/\/doi.org\/10.1139\/o59-099 (1959).","journal-title":"Can. J. Biochem. Physiol."},{"key":"87795_CR15","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0005-2760(88)90030-6","volume":"959","author":"PP Van Veldhoven","year":"1988","unstructured":"Van Veldhoven, P. P. & Bell, R. M. Effect of harvesting methods, growth conditions and growth phase on diacylglycerol levels in cultured human adherent cells. Biochim. et Biophys. Acta Lipids Lipid Metab. 959, 185\u2013196. https:\/\/doi.org\/10.1016\/0005-2760(88)90030-6 (1988).","journal-title":"Biochim. et Biophys. Acta Lipids Lipid Metab."},{"key":"87795_CR16","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1097\/00024382-200115020-00010","volume":"15","author":"GM Wray","year":"2001","unstructured":"Wray, G. M., Foster, S. J., Hinds, C. J. & Thiemermann, C. A cell wall component from pathogenic and non-pathogenic gram-positive bacteria (peptidoglycan) synergises with endotoxin to cause the release of tumour necrosis factor-alpha, nitric oxide production, shock, and multiple organ injury\/dysfunction in the rat. Shock 15, 135\u2013142 (2001).","journal-title":"Shock"},{"key":"87795_CR17","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1159\/000475298","volume":"41","author":"F Al-Rashed","year":"2017","unstructured":"Al-Rashed, F., Kochumon, S., Usmani, S., Sindhu, S. & Ahmad, R. Pam3CSK4 induces MMP-9 expression in human monocytic THP-1 cells. Cell Physiol. Biochem. 41, 1993\u20132003. https:\/\/doi.org\/10.1159\/000475298 (2017).","journal-title":"Cell Physiol. Biochem."},{"key":"87795_CR18","doi-asserted-by":"publisher","first-page":"16364","DOI":"10.1038\/s41598-020-73347-y","volume":"10","author":"S Kochumon","year":"2020","unstructured":"Kochumon, S. et al. Elevated adipose tissue associated IL-2 expression in obesity correlates with metabolic inflammation and insulin resistance. Sci. Rep. 10, 16364. https:\/\/doi.org\/10.1038\/s41598-020-73347-y (2020).","journal-title":"Sci. Rep."},{"key":"87795_CR19","doi-asserted-by":"publisher","first-page":"204201882093090","DOI":"10.1177\/2042018820930902","volume":"11","author":"S Kochumon","year":"2020","unstructured":"Kochumon, S. et al. Adipose tissue gene expression of CXCL10 and CXCL11 modulates inflammatory markers in obesity: Implications for metabolic inflammation and insulin resistance. Ther. Adv. Endocrinol. Metab. 11, 2042018820930902. https:\/\/doi.org\/10.1177\/2042018820930902 (2020).","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"87795_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081892","author":"F Al-Rashed","year":"2020","unstructured":"Al-Rashed, F. et al. Repetitive intermittent hyperglycemia drives the M1 polarization and inflammatory responses in THP-1 macrophages through the mechanism involving the TLR4-IRF5 pathway. Cells https:\/\/doi.org\/10.3390\/cells9081892 (2020).","journal-title":"Cells"},{"key":"87795_CR21","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1159\/000447798","volume":"39","author":"S Sindhu","year":"2016","unstructured":"Sindhu, S., Al-Roub, A., Koshy, M., Thomas, R. & Ahmad, R. Palmitate-induced MMP-9 expression in the human monocytic cells is mediated through the TLR4-MyD88 dependent mechanism. Cell Physiol. Biochem. 39, 889\u2013900. https:\/\/doi.org\/10.1159\/000447798 (2016).","journal-title":"Cell Physiol. Biochem."},{"key":"87795_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25204709","author":"F Al-Rashed","year":"2020","unstructured":"Al-Rashed, F., Thomas, R., Al-Roub, A., Al-Mulla, F. & Ahmad, R. LPS induces GM-CSF production by breast cancer MDA-MB-231 Cells via long-chain acyl-CoA synthetase 1. Molecules https:\/\/doi.org\/10.3390\/molecules25204709 (2020).","journal-title":"Molecules"},{"key":"87795_CR23","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8100403","author":"S Kochumon","year":"2020","unstructured":"Kochumon, S. et al. Stearic acid and TNF-alpha co-operatively potentiate MIP-1alpha production in monocytic cells via MyD88 independent TLR4\/TBK\/IRF3 signaling pathway. Biomedicines. https:\/\/doi.org\/10.3390\/biomedicines8100403 (2020).","journal-title":"Biomedicines."},{"key":"87795_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081799","author":"S Sindhu","year":"2020","unstructured":"Sindhu, S. et al. MIP-1alpha expression induced by co-stimulation of human monocytic cells with palmitate and TNF-alpha involves the TLR4-IRF3 pathway and is amplified by oxidative stress. Cells https:\/\/doi.org\/10.3390\/cells9081799 (2020).","journal-title":"Cells"},{"key":"87795_CR25","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1128\/IAI.05697-11","volume":"80","author":"HM Marriott","year":"2012","unstructured":"Marriott, H. M. et al. Interleukin-1\u03b2 regulates CXCL8 release and influences disease outcome in response to Streptococcus pneumoniae, defining intercellular cooperation between pulmonary epithelial cells and macrophages. Infect. Immun. 80, 1140\u20131149. https:\/\/doi.org\/10.1128\/IAI.05697-11 (2012).","journal-title":"Infect. Immun."},{"key":"87795_CR26","doi-asserted-by":"publisher","first-page":"e22818","DOI":"10.1371\/journal.pone.0022818","volume":"6","author":"M Chen","year":"2011","unstructured":"Chen, M., Forrester, J. V. & Xu, H. Dysregulation in retinal para-inflammation and age-related retinal degeneration in CCL2 or CCR2 deficient mice. PLoS ONE 6, e22818. https:\/\/doi.org\/10.1371\/journal.pone.0022818 (2011).","journal-title":"PLoS ONE"},{"key":"87795_CR27","first-page":"993","volume":"59","author":"Z Jamali","year":"2013","unstructured":"Jamali, Z. et al. Expression of CC chemokines CCL2, CCL5, and CCL11 is associated with duration of disease and complications in type-1 diabetes: A study on Iranian diabetic patients. Clin. Lab. 59, 993\u20131001 (2013).","journal-title":"Clin. Lab."},{"key":"87795_CR28","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.cellsig.2007.12.008","volume":"20","author":"P Gangoiti","year":"2008","unstructured":"Gangoiti, P. et al. Ceramide 1-phosphate stimulates macrophage proliferation through activation of the PI3-kinase\/PKB, JNK and ERK1\/2 pathways. Cell Signal 20, 726\u2013736. https:\/\/doi.org\/10.1016\/j.cellsig.2007.12.008 (2008).","journal-title":"Cell Signal"},{"key":"87795_CR29","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1124\/mol.108.048652","volume":"74","author":"C Graf","year":"2008","unstructured":"Graf, C. et al. Targeting ceramide metabolism with a potent and specific ceramide kinase inhibitor. Mol. Pharmacol. 74, 925\u2013932. https:\/\/doi.org\/10.1124\/mol.108.048652 (2008).","journal-title":"Mol. Pharmacol."},{"key":"87795_CR30","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/nri1184","volume":"3","author":"BB Aggarwal","year":"2003","unstructured":"Aggarwal, B. B. Signalling pathways of the TNF superfamily: A double-edged sword. Nat. Rev. Immunol. 3, 745\u2013756. https:\/\/doi.org\/10.1038\/nri1184 (2003).","journal-title":"Nat. Rev. Immunol."},{"key":"87795_CR31","doi-asserted-by":"publisher","first-page":"E713","DOI":"10.1152\/ajpendo.00194.2007","volume":"293","author":"BM De Taeye","year":"2007","unstructured":"De Taeye, B. M. et al. Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in diet-induced obesity. Am. J. Physiol. Endocrinol. Metab. 293, E713\u2013E725. https:\/\/doi.org\/10.1152\/ajpendo.00194.2007 (2007).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"87795_CR32","doi-asserted-by":"publisher","first-page":"908","DOI":"10.33594\/000000063","volume":"52","author":"R Ahmad","year":"2019","unstructured":"Ahmad, R. et al. TNF-\u03b1 drives the CCL4 expression in human monocytic cells: Involvement of the SAPK\/JNK and NF-\u03baB signaling pathways. Cell Physiol. Biochem. 52, 908\u2013921. https:\/\/doi.org\/10.33594\/000000063 (2019).","journal-title":"Cell Physiol. Biochem."},{"key":"87795_CR33","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1161\/ATVBAHA.109.198044","volume":"30","author":"H Wu","year":"2010","unstructured":"Wu, H. et al. CD11c expression in adipose tissue and blood and its role in diet-induced obesity. Arterioscler Thromb. Vasc. Biol. 30, 186\u2013192. https:\/\/doi.org\/10.1161\/ATVBAHA.109.198044 (2010).","journal-title":"Arterioscler Thromb. Vasc. Biol."},{"key":"87795_CR34","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1161\/01.HYP.0000171477.63859.b2","volume":"46","author":"M Boschmann","year":"2005","unstructured":"Boschmann, M. et al. Adipose tissue metabolism and CD11b expression on monocytes in obese hypertensives. Hypertension 46, 130\u2013136. https:\/\/doi.org\/10.1161\/01.HYP.0000171477.63859.b2 (2005).","journal-title":"Hypertension"},{"key":"87795_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19041074","author":"E Bravo-Flores","year":"2018","unstructured":"Bravo-Flores, E. et al. Macrophage populations in visceral adipose tissue from pregnant women: Potential role of obesity in maternal inflammation. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms19041074 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"87795_CR36","doi-asserted-by":"publisher","first-page":"16802","DOI":"10.1038\/s41598-020-73912-5","volume":"10","author":"F Al-Rashed","year":"2020","unstructured":"Al-Rashed, F. et al. Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes\/macrophages induced by TNF-\u03b1. Sci. Rep. 10, 16802. https:\/\/doi.org\/10.1038\/s41598-020-73912-5 (2020).","journal-title":"Sci. Rep."},{"key":"87795_CR37","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/bs.acr.2018.04.012","volume":"140","author":"A Gomez-Mu\u00f1oz","year":"2018","unstructured":"Gomez-Mu\u00f1oz, A. The role of ceramide 1-phosphate in tumor cell survival and dissemination. Adv. Cancer Res. 140, 217\u2013234. https:\/\/doi.org\/10.1016\/bs.acr.2018.04.012 (2018).","journal-title":"Adv. Cancer Res."},{"key":"87795_CR38","doi-asserted-by":"publisher","first-page":"674","DOI":"10.2174\/138945008785132349","volume":"9","author":"NF Lamour","year":"2008","unstructured":"Lamour, N. F. & Chalfant, C. E. Ceramide kinase and the ceramide-1-phosphate\/cPLA2alpha interaction as a therapeutic target. Curr. Drug Targets 9, 674\u2013682. https:\/\/doi.org\/10.2174\/138945008785132349 (2008).","journal-title":"Curr. Drug Targets"},{"key":"87795_CR39","doi-asserted-by":"publisher","first-page":"4806541","DOI":"10.1155\/2017\/4806541","volume":"2017","author":"NC Hait","year":"2017","unstructured":"Hait, N. C. & Maiti, A. The role of sphingosine-1-phosphate and ceramide-1-phosphate in inflammation and cancer. Mediat. Inflamm. 2017, 4806541. https:\/\/doi.org\/10.1155\/2017\/4806541 (2017).","journal-title":"Mediat. Inflamm."},{"key":"87795_CR40","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1194\/jlr.M084202","volume":"59","author":"B Newcomb","year":"2018","unstructured":"Newcomb, B. et al. Identification of an acid sphingomyelinase ceramide kinase pathway in the regulation of the chemokine CCL5. J. Lipid Res. 59, 1219\u20131229. https:\/\/doi.org\/10.1194\/jlr.M084202 (2018).","journal-title":"J. Lipid Res."},{"key":"87795_CR41","doi-asserted-by":"publisher","first-page":"149","DOI":"10.4161\/21623945.2014.979661","volume":"4","author":"C Bing","year":"2015","unstructured":"Bing, C. Is interleukin-1\u03b2 a culprit in macrophage-adipocyte crosstalk in obesity?. Adipocyte 4, 149\u2013152. https:\/\/doi.org\/10.4161\/21623945.2014.979661 (2015).","journal-title":"Adipocyte"},{"key":"87795_CR42","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1038\/sj.ijo.0803259","volume":"30","author":"CS Kim","year":"2006","unstructured":"Kim, C. S. et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int. J. Obes. (Lond.) 30, 1347\u20131355. https:\/\/doi.org\/10.1038\/sj.ijo.0803259 (2006).","journal-title":"Int. J. Obes. (Lond.)"},{"key":"87795_CR43","doi-asserted-by":"publisher","first-page":"703","DOI":"10.3389\/fendo.2019.00703","volume":"10","author":"J Shi","year":"2019","unstructured":"Shi, J., Fan, J., Su, Q. & Yang, Z. Cytokines and abnormal glucose and lipid metabolism. Front. Endocrinol. (Lausanne) 10, 703. https:\/\/doi.org\/10.3389\/fendo.2019.00703 (2019).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"87795_CR44","doi-asserted-by":"publisher","first-page":"e53626","DOI":"10.1371\/journal.pone.0053626","volume":"8","author":"O Nov","year":"2013","unstructured":"Nov, O. et al. Interleukin-1\u03b2 regulates fat-liver crosstalk in obesity by auto-paracrine modulation of adipose tissue inflammation and expandability. PLoS ONE 8, e53626. https:\/\/doi.org\/10.1371\/journal.pone.0053626 (2013).","journal-title":"PLoS ONE"},{"key":"87795_CR45","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1002\/hep.24599","volume":"54","author":"P Mandrekar","year":"2011","unstructured":"Mandrekar, P., Ambade, A., Lim, A., Szabo, G. & Catalano, D. An essential role for monocyte chemoattractant protein-1 in alcoholic liver injury: Regulation of proinflammatory cytokines and hepatic steatosis in mice. Hepatology 54, 2185\u20132197. https:\/\/doi.org\/10.1002\/hep.24599 (2011).","journal-title":"Hepatology"},{"key":"87795_CR46","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.3389\/fimmu.2018.01849","volume":"9","author":"JH Shi","year":"2018","unstructured":"Shi, J. H. & Sun, S. C. Tumor necrosis factor receptor-associated factor regulation of nuclear factor \u03baB and mitogen-activated protein kinase pathways. Front. Immunol. 9, 1849. https:\/\/doi.org\/10.3389\/fimmu.2018.01849 (2018).","journal-title":"Front. Immunol."},{"key":"87795_CR47","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1007\/s000180050369","volume":"55","author":"LA Tibbles","year":"1999","unstructured":"Tibbles, L. A. & Woodgett, J. R. The stress-activated protein kinase pathways. Cell Mol. Life Sci. 55, 1230\u20131254. https:\/\/doi.org\/10.1007\/s000180050369 (1999).","journal-title":"Cell Mol. Life Sci."},{"key":"87795_CR48","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1152\/physrev.00028.2011","volume":"92","author":"JM Kyriakis","year":"2012","unstructured":"Kyriakis, J. M. & Avruch, J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update. Physiol. Rev. 92, 689\u2013737. https:\/\/doi.org\/10.1152\/physrev.00028.2011 (2012).","journal-title":"Physiol. Rev."},{"key":"87795_CR49","doi-asserted-by":"publisher","first-page":"397","DOI":"10.33594\/000000028","volume":"52","author":"F Al-Rashed","year":"2019","unstructured":"Al-Rashed, F. et al. TNF-alpha induces a pro-inflammatory phenotypic shift in monocytes through ACSL1: Relevance to metabolic inflammation. Cell Physiol. Biochem. 52, 397\u2013407. https:\/\/doi.org\/10.33594\/000000028 (2019).","journal-title":"Cell Physiol. Biochem."},{"key":"87795_CR50","doi-asserted-by":"publisher","DOI":"10.3390\/biom9100555","author":"R Thomas","year":"2019","unstructured":"Thomas, R., Al-Rashed, F., Akhter, N., Al-Mulla, F. & Ahmad, R. ACSL1 regulates TNFalpha-induced GM-CSF production by breast cancer MDA-MB-231 CELLS. Biomolecules https:\/\/doi.org\/10.3390\/biom9100555 (2019).","journal-title":"Biomolecules"},{"key":"87795_CR51","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1111\/febs.13250","volume":"282","author":"J Gupta","year":"2015","unstructured":"Gupta, J. & Nebreda, A. R. Roles of p38\u03b1 mitogen-activated protein kinase in mouse models of inflammatory diseases and cancer. FEBS J. 282, 1841\u20131857. https:\/\/doi.org\/10.1111\/febs.13250 (2015).","journal-title":"FEBS J."},{"key":"87795_CR52","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1074\/jbc.M609216200","volume":"282","author":"CJ Clarke","year":"2007","unstructured":"Clarke, C. J., Truong, T. G. & Hannun, Y. A. Role for neutral sphingomyelinase-2 in tumor necrosis factor alpha-stimulated expression of vascular cell adhesion molecule-1 (VCAM) and intercellular adhesion molecule-1 (ICAM) in lung epithelial cells: p38 MAPK is an upstream regulator of nSMase2. J. Biol. Chem. 282, 1384\u20131396. https:\/\/doi.org\/10.1074\/jbc.M609216200 (2007).","journal-title":"J. Biol. Chem."},{"key":"87795_CR53","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/978-1-4419-6741-1_8","volume":"688","author":"A G\u00f3mez-Mu\u00f1oz","year":"2010","unstructured":"G\u00f3mez-Mu\u00f1oz, A., Gangoiti, P., Granado, M. H., Arana, L. & Ouro, A. Ceramide-1-phosphate in cell survival and inflammatory signaling. Adv. Exp. Med. Biol. 688, 118\u2013130. https:\/\/doi.org\/10.1007\/978-1-4419-6741-1_8 (2010).","journal-title":"Adv. Exp. Med. Biol."},{"key":"87795_CR54","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1054\/plef.1999.0100","volume":"61","author":"LC Carpio","year":"1999","unstructured":"Carpio, L. C., Stephan, E., Kamer, A. & Dziak, R. Sphingolipids stimulate cell growth via MAP kinase activation in osteoblastic cells. Prostagland. Leukot. Essent. Fatty Acids 61, 267\u2013273. https:\/\/doi.org\/10.1054\/plef.1999.0100 (1999).","journal-title":"Prostagland. Leukot. Essent. Fatty Acids"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87795-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87795-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87795-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T01:53:49Z","timestamp":1670032429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-87795-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["87795"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-87795-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-146950\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]},"assertion":[{"value":"13 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8259"}}