title: Synthesis of C-X-C and C-C chemokines by human peritoneal fibroblasts: induction by macrophage-derived cytokines.
abstract: Leukocyte accumulation during peritonitis is believed to be controlled by chemotactic factors released by resident peritoneal macrophages or mesothelial cells. Recent data indicate, however, that in many tissues fibroblasts play a key role in mediating leukocyte recruitment. We have therefore examined human peritoneal fibroblasts (HPFBs) for the expression and regulation of C-X-C and C-C chemokines. Quiescent HPFBs secreted monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 constitutively. This release could be dose-dependently augmented with the pro-inflammatory cytokines IL-1beta and tumor necrosis factor-alpha. Stimulated IL-8 production reached a plateau within 48 hours while MCP-1 continued to accumulate throughout 96 hours. Induction of IL-8 and MCP-1 synthesis by HPFBs was also triggered by peritoneal macrophage-conditioned medium. This effect was partly related to the presence of IL-1beta as demonstrated by IL-1 receptor antagonist inhibition. Pretreatment of HPFBs with actinomycin D or puromycin dose-dependently reduced cytokine-stimulated IL-8 and MCP-1 secretion, which suggested de novo chemokine synthesis. Indeed, exposure of HPFBs to IL-1beta and tumor necrosis factor-alpha produced a significant up-regulation of IL-8 and MCP-1 mRNA. This effect was associated with the rapid induction of nuclear factor-kappaB binding activity mediated through p65 and p50 subunits, and with a transient increase in the mRNA expression for RelB and inhibitory protein kappaB-alpha proteins. These data indicate that peritoneal fibroblasts are capable of generating large quantities of chemokines under a tight control of nuclear factor-kappaB/Rel transcription factors. Thus, peritoneal fibroblast-derived chemokines may contribute to the intraperitoneal recruitment of leukocytes during peritonitis.
authors: Department of Nephrology and Medical Intensive Care, Campus Berlin-Buch, Medical Faculty Charité, Humboldt-Universität zu Berlin, Berlin, Germany.
authors: J
authors: J
authors: Witowski
authors: A
authors: A
authors: Thiel
authors: R
authors: R
authors: Dechend
authors: K
authors: K
authors: Dunkel
authors: N
authors: N
authors: Fouquet
authors: T O
authors: TO
authors: Bender
authors: J M
authors: JM
authors: Langrehr
authors: G M
authors: GM
authors: Gahl
authors: U
authors: U
authors: Frei
authors: A
authors: A
authors: Jörres
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D019742:Chemokines, CC / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011994:Recombinant Proteins; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D018932:Chemokine CCL2; D019742:Chemokines, CC; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D016207:Cytokines; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D011994:Recombinant Proteins; D014157:Transcription Factors; D051841:Transcription Factor RelB