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Moreover, the expression of matrix metalloproteinase-1 (MMP-1) from involved scleroderma skin fibroblasts is refractory to stimulation by tumour necrosis factor (TNF)-\u03b1. To elucidate the mechanism(s) involved, we examined the effect of IL-13 on TNF-\u03b1-induced MMP-1 expression in normal and scleroderma human dermal fibroblast lines and studied the involvement of serine\/threonine kinase B\/protein kinase B (Akt) in this response. Dermal fibroblast lines were stimulated with TNF-\u03b1 in the presence of varying concentrations of IL-13. Total Akt and pAkt were quantitated using Western blot analyses. Fibroblasts were treated with or without Akt inhibitor VIII in the presence of IL-13 followed by TNF-\u03b1 stimulation. MMP-1 expression was analysed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using analysis of variance (anova) or Student's t-test. Upon TNF-\u03b1 stimulation, normal dermal fibroblasts secrete more MMP-1 than systemic sclerosis (SSc) fibroblasts. This increase in MMP-1 is lost when fibroblasts are co-incubated with IL-13 and TNF-\u03b1. IL-13 induced a significant increase in levels of pAkt in dermal fibroblasts, while Akt inhibitor VIII reversed the suppressive effects of IL-13 on the response of cultured fibroblasts to TNF-\u03b1, increasing their expression of MMP-1. We show that IL-13 suppresses MMP-1 in TNF-\u03b1-stimulated normal and scleroderma dermal fibroblast. Akt inhibitor VIII is able to reverse the suppressive effect of IL-13 on MMP-1 expression and protein synthesis. Our data suggest that IL-13 regulates MMP-1 expression in response to TNF-\u03b1 through an Akt-mediated pathway and may play a role in fibrotic diseases such as scleroderma.<\/jats:p>","DOI":"10.1111\/cei.13045","type":"journal-article","created":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T03:36:44Z","timestamp":1504841804000},"page":"84-95","source":"Crossref","is-referenced-by-count":11,"title":["Chronic exposure of interleukin-13 suppress the induction of matrix metalloproteinase-1 by tumour necrosis factor \u03b1 in normal and scleroderma dermal fibroblasts through protein kinase B\/Akt"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0362-9299","authenticated-orcid":false,"given":"M L","family":"Brown Lobbins","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Tennessee Health Science Center, Division of Connective Tissue Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B R","family":"Shivakumar","sequence":"additional","affiliation":[{"name":"Veterans Administration Medical Center, Memphis, Tennessee"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A E","family":"Postlethwaite","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Connective Tissue Diseases, University of Tennessee Health Science Center, Veterans Administration Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K A","family":"Hasty","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Division of Connective Tissue Diseases, University of Tennessee Health Science Center, Veterans Administration Medical 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