title: Interleukin-36α Induces Inflammatory Mediators From Human Pancreatic Myofibroblasts Via a MyD88 Dependent Pathway.
abstract: Interleukin-36 (IL-36) is a recently described proinflammatory cytokine, characterized by the induction of inflammatory mediators. In the present study, we investigated the biological activity and the signal transduction of IL-36α in human pancreatic myofibroblasts.
  
  
  
  The mRNA and protein expression of inflammatory mediators was evaluated using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of IL-36α and its receptor in the pancreatic tissue was evaluated using immunohistochemical technique. Intracellular signaling pathways were evaluated using immunoblotting and specific small interference RNA-transfected cells.
  
  
  
  Interleukin-36α and its receptor complex IL-36R/IL-1RAcP were detected in fibrotic tissue of chronic pancreatitis. Interleukin-36α dose- and time-dependently induced the mRNA expression and protein secretion of CXCL1, CXCL8, MMP-1, and MMP-3 from human pancreatic myofibroblasts. Interleukin-36α assembled MyD88 adaptor proteins (MyD88, TRAF6, IRAK1, and TAK1) into a complex. Furthermore, IL-36α induced the phosphorylation of mitogen-activated protein kinases and the activation of nuclear factor κB and activator protein 1. Mitogen-activated protein kinase inhibitors and small interference RNAs specific for nuclear factor κB and activator protein 1 significantly suppressed the protein secretion of inflammatory mediators induced by IL-36α stimulation.
  
  
  
  It was suggested that IL-36α plays an important role in the pathophysiology of inflammation and fibrosis in the pancreas via an autocrine function.
authors.affiliation: From the Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.forename: Osamu
authors.initials: O
authors.lastname: Inatomi
authors.forename: Takehide
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Masaji
authors.initials: M
authors.lastname: Tani
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D058628:Myofibroblasts / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D053594:Myeloid Differentiation Factor 88; D018123:Receptors, Interleukin; C572887:interleukin 36, human; C571244:interleukin-36 receptor, human