{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:21Z","timestamp":1787026521672,"version":"build-2736575974"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Interleukin-6 (IL-6) is an important player in chronic inflammation associated with heart failure and tumor-induced cachexia. Fibroblasts are salient mediators of both inflammation and fibrosis. Whereas the general outcome of IL-6 on the heart\u2019s function and muscle wasting has been intensively studied, the influence of IL-6 on fibroblasts of the heart and skeletal muscle (SM) has not been analyzed so far. We illustrate that SM-derived fibroblasts exhibit higher basal mRNA expression of \u03b1-SMA, extracellular matrix molecules (collagen1a1\/3a1\/5a1), and chemokines (CCL2, CCL7, and CX3CL1) as compared to the left ventricle (LV)-derived fibroblasts. IL-6 drives the transdifferentiation of fibroblasts into myofibroblasts as indicated by an increase in \u03b1-SMA expression and upregulates NLRP3 inflammasome activity in both LV- and SM-derived fibroblasts. IL-6 increases the release of CCL7 to CX3CL1 in the supernatant of SM-derived fibroblasts associated with the attraction of more pro(Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    ) versus anti(Ly6C\n                    <jats:sup>lo<\/jats:sup>\n                    ) inflammatory monocytes as compared to unstimulated fibroblasts. IL-6-stimulated LV-derived fibroblasts attract less Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    to Ly6C\n                    <jats:sup>lo<\/jats:sup>\n                    monocytes compared to IL-6-stimulated SM-derived fibroblasts. In addition, SM-derived fibroblasts have a higher mitochondrial energy turnover and lower glycolytic activity versus LV-derived fibroblasts under basal and IL-6 conditions. In conclusion, IL-6 modulates the inflammatory and metabolic phenotype of LV- and SM-originated fibroblasts.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.947267","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T03:01:05Z","timestamp":1658977265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Left ventricle- and skeletal muscle-derived fibroblasts exhibit a differential inflammatory and metabolic responsiveness to 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