Transcriptional regulation of inflammatory mediators secreted by human colonic circular smooth muscle cells.
We investigated the transcriptional regulation of secretion of pro- and anti-inflammatory mediators by human colonic circular smooth muscle cells (HCCSMC) in response to tumor necrosis factor (TNF)-alpha. Gene chip array analysis indicated that HCCSMC express a specific panel of 11 cytokines, chemokines, and cell adhesion molecules in a time-dependent manner in response to TNF-alpha. The chip array data were supported by quantitative analysis of mRNA and protein expressions of interleukin (IL)-6, IL-8, intercellular adhesion molecule (ICAM)-1 and IL-11. The proinflammatory mediators were expressed early, whereas the anti-inflammatory cytokine IL-11 was expressed late after TNF-alpha treatment. The expression of ICAM-1 on HCCSMC increased lymphocyte adhesion to these cells, which was blocked by pretreatment with antibody to ICAM-1. TNF-alpha acted on both R(1) and R(2) receptors to induce the expression of ICAM-1. Pretreatment of HCCSMC with antisense oligonucleotides to p65 nuclear factor-kappaB (NF-kappaB) blocked the expression of ICAM-1, whereas pretreatment with antisense oligonucleotides to p50 NF-kappaB had little effect. The overexpression of p65 NF-kappaB enhanced the constitutive expression of ICAM-1, and TNF-alpha treatment had no further effect. The delayed expression of endogenous IL-11 limited the expression of ICAM-1, and pretreatment of HCCSMC with antisense oligonucleotides to IL-11 enhanced it. We conclude that TNF-alpha induces gene expression in HCCSMC for programmed synthesis and release of pro- and anti-inflammatory mediators.
Shi
Xuan-Zheng
XZ
Division of Gastroenterology, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, 9.138 Medical Research Bldg., Galveston, TX 77555-1064, USA.
Sarna
Sushil K
SK
D002448:Cell Adhesion / Q000276:immunology; D003106:Colon / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology; D051996:Transcription Factor RelA; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018836:Inflammation Mediators; D017370:Interleukin-11; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1