title: Peroxynitrite enhances interleukin-10 reduction in the release of neutrophil chemotactic activity.
abstract: Peroxynitrite, formed by nitric oxide and superoxide, has been shown to nitrate and reduce the function of proinflammatory proteins such as interleukin (IL)-8, monocyte chemoattractant protein-1, and eotaxin, but in contrast, to enhance the function of the anti-inflammatory cytokine IL-10 in reducing IL-1 release from blood monocytes. However, the effect of nitrated IL-10 on release of proinflammatory cytokines from lung epithelial cells is unknown. We hypothesized that peroxynitrite would enhance the capacity of human IL-10 to reduce inflammatory mediators released by epithelial cells. To test this hypothesis, recombinant human IL-10 was evaluated for its capacity to attenuate the release of neutrophil chemotactic activity and IL-8 from a human epithelial cell line in response to IL-1 beta and tumor necrosis factor-alpha. Neutrophil chemotactic activity and IL-8 in lung epithelial culture supernatant fluids were significantly lower after culture with nitrated human IL-10 compared with non-nitrated human IL-10 controls (P < 0.05). Consistent with these results, nitrated human IL-10 attenuated IL-8 mRNA expression more than non-nitrated human IL-10 controls (P < 0.05). These data demonstrate that peroxynitrite exposed human IL-10 has enhanced anti-inflammatory activity and suggest that nitration may play a critical role in the regulation of inflammation within the lower respiratory tract.
authors.affiliation: Research Service Line, Southern Arizona Veterans Health Care System, and Arizona Respiratory Center, University of Arizona, Tucson, AZ 85723, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Numanami
authors.forename: Dan K
authors.initials: DK
authors.lastname: Nelson
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Hoyt
authors.forename: Jon L
authors.initials: JL
authors.lastname: Freels
authors.forename: Michael
authors.initials: M
authors.lastname: Habib
authors.forename: Jun
authors.initials: J
authors.lastname: Amano
authors.forename: Masayuki
authors.initials: M
authors.lastname: Haniuda
authors.forename: Sekiya
authors.initials: S
authors.lastname: Koyama
authors.forename: Richard A
authors.initials: RA
authors.lastname: Robbins
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D002633:Chemotaxis; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012137:Respiratory System / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D030421:Peroxynitrous Acid; D009584:Nitrogen