{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:48Z","timestamp":1787028468279,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003500","name":"University of Padua","doi-asserted-by":"publisher","award":["UNIPD-DSF-DOR founds to A.P., R.F. and M.Z."],"award-info":[{"award-number":["UNIPD-DSF-DOR founds to A.P., R.F. and M.Z."]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The blue-green alga Spirulina platensis is rich in phycocyanins, that exhibit a wide range of pharmacological actions. C-phycocyanin (C-PC), in particular, possesses hepatoprotective, nephroprotective, antioxidant, and anticancer effects. Furthermore, several studies have reported both anti- and proinflammatory properties of this pigment. However, the precise mechanism(s) of action of C-PC in these processes remain largely unknown. Therefore, here we explored the C-PC effect in in vitro microglia activation. The effect of C-PC on the expression and release of IL-1\u03b2 and TNF-\u03b1 and the activation of NF-\u03baB was examined in primary microglia by real-time PCR, ELISA, and immunofluorescence. Treatment with C-PC up-regulated the expression and release of IL-1\u03b2 and TNF-\u03b1. C-PC also promoted the nuclear translocation of the NF-\u03baB transcription factor. Then, to elucidate the molecular mechanisms for the immunoregulatory function of C-PC, we focused on investigating the role of Toll-like receptor 4 (TLR4). Accordingly, several TLR4 inhibitors have been used. Curcumin, ciprofloxacin, L48H37, and CLI-095 that suppresses specifically TLR4 signaling, blocked IL-1\u03b2 and TNF-\u03b1. Overall, these results indicate the immunomodulatory effect of C-PC in microglia cultures and show for the first time that the molecular mechanism implicated in this effect may involve TLR4 activation.<\/jats:p>","DOI":"10.3390\/ijms23031440","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T22:00:56Z","timestamp":1643320856000},"page":"1440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Effect of C-Phycocyanin on Microglia Activation Is Mediated by Toll-like Receptor 4"],"prefix":"10.3390","volume":"23","author":[{"given":"Anna","family":"Piovan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Filippini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Argentini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-3802","authenticated-orcid":false,"given":"Stefano","family":"Moro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Giusti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morena","family":"Zusso","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.algal.2013.12.004","article-title":"Aqueous extraction of proteins from microalgae: Effect of different cell disruption methods","volume":"3","author":"Safi","year":"2014","journal-title":"Algal Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.2174\/138920108785915111","article-title":"Spirulina in health care management","volume":"9","author":"Kulshreshtha","year":"2008","journal-title":"Curr. 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