title: Inflammatory cytokines mediate C-C (monocyte chemotactic protein 1) and C-X-C (interleukin 8) chemokine expression in human pleural fibroblasts.
abstract: Current knowledge implicates pleural mesothelial cells as mainly responsible for inflammatory responses in the pleural space. However, a vast body of recent evidence underscores the important role of fibroblasts in the process of inflammation in several types of tissues. We hypothesize that HPFBs (human pleural fibroblasts) play an important role in pleural responses and also when activated by bacterial endotoxin LPS (lipopolysaccharide), IL-1 beta (interleukin-1 beta), or TNF-alpha (tumor necrosis factor-alpha) release of C-C and C-X-C chemokines-specifically, MCP-1 and IL-8. Our results show that pleural fluid-isolated human fibroblasts release IL-8 and MCP-1 upon stimulation with IL-1 beta, TNF-alpha, and LPS in both a concentration- and time-dependent manner. RT-PCR (reverse-transcriptase-polymerase chain reaction) studies have also confirmed IL-8- and MCP-1-specific mRNA expression in activated pleural fibroblasts. On the time-dependent response curve, IL-8 was found in maximum concentrations at 144 hr, whereas MCP-1 continued to increase even after 196 hr following stimulation. IL-1 beta induced the maximum release of IL-8 (800-fold) and MCP-1 (164-fold), as compared to the controls. TNF-alpha induced a 95-fold increase in IL-8 and an 84-fold increase in MCP-1 levels, as compared to the controls. Collectively, our results show that human pleural fibroblasts contribute to the inflammatory cascade in the pleural space.
authors: Division of Pulmonary and Critical Care Medicine, Veterans' Affairs Medical Center, Indiana University School of Medicine, Indianapolis 46202, USA.
authors: Farzad
authors: F
authors: Loghmani
authors: Kamal A
authors: KA
authors: Mohammed
authors: Najmunnisa
authors: N
authors: Nasreen
authors: Robert D
authors: RD
authors: Van Horn
authors: Joyce A
authors: JA
authors: Hardwick
authors: Kerry L
authors: KL
authors: Sanders
authors: Veena B
authors: VB
authors: Antony
mesh_terms: D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010994:Pleura / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D018076:DNA, Complementary; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha