title: Influence of the anti-inflammatory cytokine interleukin-4 on human joint capsule myofibroblasts.
abstract: Post-traumatic joint contracture was reported to be associated with elevated numbers of contractile myofibroblasts (MFs) in the healing capsule. During the physiological healing process, the number of MFs declines; however, in fibroconnective disorders, MFs persist. The manifold interaction of the cytokines regulating the appearance and persistence of MFs in the pathogenesis of joint contracture remains to be elucidated. The objective of our current study was to analyze the impact of the anti-inflammatory cytokine interleukin (IL)-4 on functional behavior of MFs. Cells were isolated from human joint capsule specimens and challenged with three different concentrations of IL-4 with or without its neutralizing antibody. MF viability, contractile properties, and the gene expression of both alpha-smooth muscle actin (α-SMA) and collagen type I were examined. Immunofluorescence staining revealed the presence of IL-4 receptor (R)-alpha (α) on the membrane of cultured MFs. The cytokine IL-4 promoted MF viability and enhanced MF modulated contraction of collagen gels. Moreover, IL-4 intervened in gene expression by up-regulation of α-SMA and collagen type I mRNA. These effects could be specifically lowered by the neutralizing IL-4 antibody. On the basis of our findings we conclude that the anti-inflammatory cytokine IL-4 specifically regulates viability and the contractile properties of MFs via up-regulating the gene expression of α-SMA and collagen type I. IL-4 may be a helpful target in developing anti-fibrotic therapeutics for post-traumatic joint contracture in human. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1290-1298, 2017.
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Stefan G
authors: SG
authors: Mattyasovszky
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Stefan
authors: S
authors: Mausbach
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Ulrike
authors: U
authors: Ritz
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Eva
authors: E
authors: Langendorf
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Jochen
authors: J
authors: Wollstädter
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Andreas
authors: A
authors: Baranowski
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Phillipp
authors: P
authors: Drees
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Pol Maria
authors: PM
authors: Rommens
authors: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
authors: Alexander
authors: A
authors: Hofmann
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism; D017746:Joint Capsule / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000502:physiology*; D061251:Primary Cell Culture
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; C508598:IL4 protein, human; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D015847:Interleukin-4
keywords: interleukin-4; myofibroblast; post-traumatic joint contracture