Cyclooxygenase-2 Inhibitor SC-236 [4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] Benzenesulfonamide] Suppresses Nuclear Factor-κB Activation and Phosphorylation of p38 Mitogen-Activated Protein Kinase, Extracellular Signal-Regulated Kinase, and c-Jun N-Terminal Kinase in Human Mast Cell Line Cells

Kim, Sujin; Jeong, Hyun‐Ja; Choi, In-Mook; Lee, Kang‐Min; Park, Raekil; Hong, Seung‐Heon; Kim, Hyung-Min

doi:10.1124/jpet.104.082792

Cited by 21 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the study by Dogan et al (20), such a blockade occurred only when the dose of SC-236 was substantially higher (40 mg/kg) than the doses (1-15 mg/kg) known to selectively block COX-2 in vivo (31,53). At such a high dose, SC-236 might have inhibited COX-1, or it might have exerted COX-unrelated effects (39). Although the study by Zhang et al (90) employed a lower dose of SC-236 (5 mg/kg), it was limited by marked stress hyperthermia following intraperitoneal drug administration, which overlapped substantially with the early hypothermic response to LPS, thus making the results difficult to interpret.…”

Section: Effects Of Cox-1 and Cox-2 Inhibitors On Lps-induced Responsesmentioning

confidence: 99%

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Steiner

Hunter²,

Phipps³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

DL, Romanovsky AA. Cyclooxygenase-1 or -2-which one mediates lipopolysaccharide-induced hypothermia? Am J Physiol Regul Integr Comp Physiol 297: R485-R494, 2009. First published June 10, 2009 doi:10.1152/ajpregu.91026.2008.-Systemic inflammation is associated with either fever or hypothermia. Fever, a response to mild systemic inflammation, is mediated by cyclooxygenase (COX)-2 and not by COX-1. However, it is still disputed whether COX-2, COX-1, neither, or both mediate(s) responses to severe systemic inflammation, and, in particular, the hypothermic response. We compared the effects of SC-236 (COX-2 inhibitor) and SC-560 (COX-1 inhibitor) on the deep body temperature (Tb) of rats injected with a lower (10 g/kg iv) or higher (1,000 g/kg iv) dose of LPS at different ambient temperatures (Tas). At a neutral Ta (30°C), the rats responded to LPS with a polyphasic fever (lower dose) or a brief hypothermia followed by fever (higher dose). SC-236 (2.5 mg/kg iv) blocked the fever induced by either LPS dose, whereas SC-560 (5 mg/kg iv) altered neither the febrile response to the lower LPS dose nor the fever component of the response to the higher dose. However, SC-560 blocked the initial hypothermia caused by the higher LPS dose. At a subneutral T a (22°C), the rats responded to LPS with early (70 -90 min, nadir) dose-dependent hypothermia. The hypothermic response to either dose was enhanced by SC-236 but blocked by SC-560. The hypothermic response to the higher LPS dose was associated with a fall in arterial blood pressure. This hypotensive response was attenuated by either SC-236 or SC-560. At the onset of LPS-induced hypothermia and hypotension, the functional activity of the COX-1 pathway (COX-1-mediated PGE2 synthesis ex vivo) increased in the spleen but not liver, lung, kidney, or brain. The expression of splenic COX-1 was unaffected by LPS. We conclude that COX-1, but not COX-2, mediates LPS hypothermia, and that both COX isoforms are required for LPS hypotension. body temperature; thermoregulation; fever; inflammation SO STRONGLY IS SYSTEMIC INFLAMMATION associated with changes in deep body temperature (T b ) that every clinical definition of the systemic inflammatory response syndrome includes a change in T b (11,48). Whereas the majority (ϳ90%) of patients with systemic inflammation have an increased T b , a number of them (ϳ10%) have a lowered T b (6, 17). Thermoregulatory manifestations are also present in animal models of systemic inflammation. In a rat model of systemic inflammation induced by bacterial LPS, the pattern of T b change depends on the ambient temperature (T a ) and the LPS dose. At a neutral or supraneutral T a (warm environment), fever is the prevailing response; the fever is monophasic when the dose of LPS is low (just suprathreshold), but it turns polyphasic as the dose increases (66, 68, 69, 71, 79); a mild hypothermia may precede the polyphasic fever when the dose of LPS is high (68). At a subneutral T a (cool environment), hypothermia followed by fever is the predominant response; th...

show abstract

Section: Effects Of Cox-1 and Cox-2 Inhibitors On Lps-induced Responsesmentioning

confidence: 99%

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Steiner

Hunter²,

Phipps³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…69 -71 These intracellular pathways have also been shown to play a significant role in smooth muscle cells, mast cells, and endothelial cells. [72][73][74] Hence, the expression of PGE 2 -synthesizing enzymes is most likely regulated by a complex network of cytokines and signal transduction pathways, as well as by cross-talk interactions among cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of Prostaglandin E Synthases in Periodontitis

Båge

Kats

Lopez

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

The inflammatory mediator prostaglandin E 2 (PGE 2 ) is implicated in the pathogenesis of chronic inflammatory diseases including periodontitis; it is synthesized by cyclooxygenases (COX) and the prostaglandin E synthases mPGES-1, mPGES-2, and cPGES. The distribution of PGES in gingival tissue of patients with periodontitis and the contribution of these enzymes to inflammationinduced PGE 2 synthesis in different cell types was investigated. In gingival biopsies, positive staining for PGES was observed in fibroblasts and endothelial, smooth muscle, epithelial, and immune cells. To further explore the contribution of PGES to inflammation-induced PGE 2 production, in vitro cell culture experiments were performed using fibroblasts and endothelial, smooth muscle, and mast cells. All cell types expressed PGES and COX-2, resulting in basal levels of PGE 2 synthesis. In response to tumor necrosis factor (TNF-␣), IL-1␤, and cocultured lymphocytes, however, mPGES-1 and COX-2 protein expression increased in fibroblasts and smooth muscle cells, accompanied by increased PGE 2 , whereas mPGES-2 and cPGES were unaffected. In endothelial cells, TNF-␣ increased PGE 2 production only via COX-2 expression, whereas in mast cells the cytokines did not affect PGE 2 enzyme expression or PGE 2 production. Furthermore, PGE 2 production was diminished in gingival fibroblasts derived from mPGES-1 knockout mice, compared with wild-type fibroblasts. These results suggest that fibroblasts and smooth muscle cells are important sources of mPGES-1, which may contribute to increased PGE 2 production in the inflammatory condition periodontitis.

show abstract

“…27,28 Several studies suggested that suppression of MC NF-kB is responsible for reducing inflammatory mediators released during inflammation. [29][30][31] Thus we asked whether iTreg cells can modulate NF-kB signaling in MCs. To this end, BMMCs were cocultured with iTreg cells (2:1 ratio) for 24 hours, followed by stimulation with PMACI for another 6 hours.…”

Section: Itreg Cells Inhibit Proinflammatory Cytokine Release In Mcs mentioning

confidence: 99%

Induced CD4+ forkhead box protein–positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1

Fan

Chen

et al. 2012

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Cited by 21 publications

References 36 publications

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Expression of Prostaglandin E Synthases in Periodontitis

Induced CD4+ forkhead box protein–positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1

Contact Info

Product

Resources

About