title: Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance.
abstract: Inflammatory signals induce feedback and feedforward systems that provide temporal control. Although glucocorticoids can repress inflammatory gene expression, glucocorticoid receptor recruitment increases expression of negative feedback and feedforward regulators, including the phosphatase, DUSP1, the ubiquitin-modifying enzyme, TNFAIP3, or the mRNA-destabilizing protein, ZFP36. Moreover, glucocorticoid receptor cooperativity with factors, including nuclear factor-κB (NF-κB), may enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, provide feedforward control to limit expression of the transcription factor IRF1, and the chemokine, CXCL10. We propose that modulation of feedback and feedforward control can determine repression or resistance of inflammatory gene expression toglucocorticoid.
authors.affiliation: From the Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Alberta T2N 4Z6, Canada, rnewton@ucalgary.ca.
authors.forename: Robert
authors.identifier: 0000-0002-4919-8498
authors.initials: R
authors.lastname: Newton
authors.affiliation: the Arnie Charbonneau Cancer Institute, Department of Oncology, University of Calgary, Alberta T2N 4Z6, Canada.
authors.forename: Suharsh
authors.initials: S
authors.lastname: Shah
authors.affiliation: From the Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Alberta T2N 4Z6, Canada.|the Faculty of Science, Sohag University, Sohag 82524, Egypt, and.
authors.forename: Mohammed O
authors.initials: MO
authors.lastname: Altonsy
authors.affiliation: the Department of Medicine, National Jewish Health, Denver, Colorado 80206.
authors.forename: Antony N
authors.initials: AN
authors.lastname: Gerber
mesh_terms: D000072283:A549 Cells; D000818:Animals; D054357:Chemokine CXCL10 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D051816:Tristetraprolin / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000378:metabolism
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D005938:Glucocorticoids; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; C498143:RELA protein, human; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D051996:Transcription Factor RelA; D051816:Tristetraprolin; C497552:ZFP36 protein, human; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: gene expression; gene regulation; glucocorticoid; glucocorticoid receptor; inflammation