Endoplasmic Reticulum Stress-activated C/EBP Homologous Protein Enhances Nuclear Factor-κB Signals via Repression of Peroxisome Proliferator-activated Receptor γ

• DOI: 10.1074/jbc.m110.136259
• Publication Date: 2010-09-10T04:14:43Z
• Authors: Seong-Hwan Park; Hye Jin Choi; Hyun Yang; Kee Hun Do; Juil Kim; Dong Won Lee; Yuseok Moon
• Keywords: Chromatin Immunoprecipitation; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; CCAAT-Enhancer-Binding Protein-beta; Blotting, Western; Interleukin-8; NF-kappa B; Enzyme-Linked Immunosorbent Assay; Endoplasmic Reticulum; HCT116 Cells; PPAR gamma; 03 medical and health sciences; Cell Line, Tumor; Humans; HT29 Cells; Transcription Factor CHOP; Protein Binding; Signal Transduction

Endoplasmic reticulum (ER) stress is a causative factor of inflammatory bowel diseases. ER mediators, including CCAAT enhancer-binding protein (C/EBP) homologous (CHOP), are elevated in intestinal epithelia from patients with The present study arose the question how chemical and CHOP were associated nuclear factor-κB (NF-κB)-mediated epithelial response. In human cell culture model, stresses induced proinflammatory cytokine interleukin-8 (IL-8) expression translocation protein. was positively involved ER-activated IL-8 production negatively peroxisome proliferator-activated receptor γ (PPARγ). stress-induced enhanced by NF-κB activation that regulated PPARγ. Mechanistically, suppressed PPARγ transcription sequestering C/EBPβ limiting availability binding to promoter. Due CHOP-mediated regulation action, can enhance maintain an increased level cells. contrast, counteracting regulator gut response through attenuation activation. collective results support view balances between crucial for homeostasis, disruption these mucosal etiologically affect progress IntroductionEndoplasmic 2The abbreviations used are: ERendoplasmic reticulumC/EBPCCAAT proteinCHOPC/EBP proteindnCHOPdominant negative CHOPIBDinflammatory disease(s)PPARγperoxisome γTGthapsigarginNF-κBnuclear factor-κBIRE1inositol-requiring ER-to-nucleus signal kinase 1PERKRNA-dependent kinase-like kinaseATF6activating 6. biosynthesis organelle which newly synthesized proteins accurately folded into their proper conformation. However, under diverse pathological stress, folding may occur improperly, or unfold; aberrant trigger severe called (1Kopito R.R. Trends Cell Biol. 2000; 10: 524-530Abstract Full Text PDF PubMed Scopus (1583) Google Scholar). 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Lai M.D. 2004; 279: 46384-46392Abstract (200) IRE1 interacts C terminus TNF receptor-associated 2, involves (41Kaneko Niinuma Nomura Pharm. Bull. 2003; 26: 931-935Crossref (208) PERK activates phosphorylation eIF2α, inhibiting translation. triggers 2 α 4, another (39Jiang Wek McGrath B.C. Scheuner Kaufman R.J. Cavener D.R. 5651-5663Crossref (350) ATF6 B pathway. chronic 42Kahle Haass EMBO Rep. 5: 681-685Crossref (110) 43Araki Intern. 42: 7-14Crossref (136) Particularly epithelia, X-box confers genetic susceptibility (9Kaser Scholar).Because occurs earlier maintaining whole process. Early other IRE1, PERK, ATF6. Instead, presently maintenance low levels epithelia. Without action cells, strongly up-regulated, abolished Therefore, expected mediator prolonged insults addition, partly death (supplemental Fig. S2, A B). Chemical inducers, TG tunicamycin, at higher doses those caused death, rather acute 44Jorgensen Stinson Shan Yang Gietl Albino A.P. 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Brüne 681-694Crossref (71) Whereas suppress enhancing study, explanation snatching (50Zwergal Quirling Saugel Huth K.C. Sydlik Poli Neumeier Ziegler-Heitbrock H.W. Brand 177: 665-672Crossref lipopolysaccharide delays PPARγ, oxidative ribotoxic (51Moon Park S.H. Toxicol. Appl. Pharmacol. 231: 94-102Crossref (28) 52Von A.A. FASEB 2001; 535-544Crossref (69) although increases colon cancers, it not always bad news terms defense infection. mechanical injury models, wound healing responses, particular promoting proliferation (53Ishida Kondo Kimura Matsushima Mukaida 5598-5606Crossref (134) 54Egan L.J. de Lecea Lehrman E.D. Myhre G.M. Eckmann Kagnoff M.F. Physiol. 285: C1028-C1035Crossref (76) promotes reconstitution injured monolayer genes, inducible nitric-oxide synthase cyclooxygenase-2, strong migration site (55Noiri Peresleni Srivastava Weber Bahou W.F. Peunova Goligorsky M.S. 270: C794-C802Crossref 56Cowan M.J. Coll Shelhamer 101: 1127-1135Crossref (11) Thus, speculated stress-activated protect toxic even facilitates process after lessen (57Fukata Michelsen Eri Thomas L.S. Hu Lukasek Nast Lechago Xu Naiki Soliman Arditi Abreu M.T. Gastrointest. Liver 288: G1055-G1065Crossref (418) more careful observations needed homeostatic counteraction activated PPARγ-mediated particular, promising insight mechanism decision assessed.