title: Evidence for the involvement of distinct signal transduction pathways in the regulation of constitutive and interferon gamma-dependent gene expression of NADPH oxidase components (gp91-phox, p47-phox, and p22-phox) and high-affinity receptor for IgG (Fc gamma R-I) in human polymorphonuclear leukocytes.
abstract: We recently showed that mRNA levels coding the high-affinity Fc gamma receptor for IgG (Fc gamma R-I, CD64) and two of the components of the phagocytic superoxide anion-generating system--the heavy-chain subunit of cytochrome b558 (gp91-phox) and the 47-Kd cytosolic factor (p47-phox)--are modulated by interferon gamma (IFN-gamma). In this study, we examined whether dexamethasone (DEX) affects gp91-phox and p47-phox mRNA expression of human polymorphonuclear leukocytes (PMN), treated or not with IFN-gamma. We also investigated whether staurosporine, a general inhibitor of protein kinases, influences gp91-phox, p47-phox, and Fc gamma R-I gene expression in PMN treated with or without IFN-gamma. We found that (1) gp91-phox mRNA steady-state levels, expressed in control or IFN-gamma-treated PMN, were significantly inhibited, in a dose-dependent fashion, by both DEX and staurosporine; (2) p47-phox mRNA steady-state levels, expressed in control or IFN-gamma-treated PMN, were not influenced by DEX, but were markedly depressed by staurosporine; (3) no changes of spectrophotometric cytochrome b558 were found in PMN treated for up to 20 hours with the inhibitors, regardless of the presence of IFN-gamma; (4) both DEX and staurosporine dose-dependently inhibited IFN-gamma-induced Fc gamma R-I mRNA and protein expression; and (5) stability of gp91-phox and Fc gamma R-I messages in IFN-gamma-treated PMN was not altered by the presence of DEX. Our results demonstrate that gp91-phox, p47-phox, and Fc gamma R-I gene expression of PMN is governed by specific and independent biochemical pathways. Moreover, IFN-gamma activates different signal transduction pathways to modulate mRNA expression of gp91-phox, p47-phox, and Fc gamma R-I.
authors.affiliation: Institute of General Pathology, University of Verona, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Amezaga
authors.forename: F
authors.initials: F
authors.lastname: Bazzoni
authors.forename: C
authors.initials: C
authors.lastname: Sorio
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: M A
authors.initials: MA
authors.lastname: Cassatella
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000235:genetics*; D015152:Blotting, Northern; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000235:genetics; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011961:Receptors, Fc / Q000235:genetics*; D017452:Receptors, IgG; D011994:Recombinant Proteins; D015398:Signal Transduction; D019311:Staurosporine; D013997:Time Factors
chemical_list: D000470:Alkaloids; D000943:Antigens, Differentiation; D003573:Cytochrome b Group; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D003907:Dexamethasone; D007371:Interferon-gamma; C036888:cytochrome b558; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D019311:Staurosporine