Suppressive effects of tranilast on the expression of inducible cyclooxygenase (COX2) in interleukin-1β-stimulated fibroblasts

Inone, Hajime; Ohshima, Hideo; Kono, Hiroyuki; Yamanaka, Miwa; Kubota, Takako; Aihara, Masaki; Hiroi, Tomoko; Yago, Nagasumi; Ishida, Hirotomo

doi:10.1016/s0006-2952(97)00187-1

Cited by 31 publications

(15 citation statements)

References 12 publications

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“…The mast-cell product responsible for this action was thought to be IL-4. Other reports indicated that IL-1␤ (13) or secretory phospholipase A (14) are involved in COX2 induction and PG synthesis. Importantly, it seems that PGs, including PGD 2 , can regulate fibroblast proliferation and type I collagen production (15,16).…”

mentioning

confidence: 99%

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Frungieri

Weidinger

Meineke

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

238

229

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Mast-cell products can stimulate fibroblast proliferation, implying that these cells are key players in fibrosis. One mast-cell product, the serine protease tryptase, is known to activate protease-activated receptor 2 (PAR2) and cause proliferation of fibroblasts. We found that recombinant tryptase, human mastcell (HMC-1) supernatant, which contains tryptase, and the PAR2-activating peptide SLIGKV exert fibroproliferative actions in human fibroblasts. Here we report insights into this action, which after activation of PAR2 leads to increased expression of cyclooxygenase 2 (COX2), a key enzyme in the biosynthesis of prostaglandins, and consequently to enhanced prostaglandin synthesis. Subsequent cell proliferation is mediated by the prostaglandin 15-deoxy-⌬ 12,14 -prostaglandin J2, which acts via the nuclear peroxisome proliferator-activated receptor ␥ (PPAR␥). Fibroblast proliferation induced by tryptase and PAR2 agonist peptide can be blocked by antagonists of COX2 and PPAR␥, implying that the proliferative effect of tryptase is PAR2-initiated but depends on COX2, 15-deoxy-⌬ 12,14 -prostaglandin J2, and PPAR␥. This previously uncharacterized pathway could be of relevance for human fibrotic diseases. For instance, increased numbers of activated mast cells are correlated with fibrosis in testes of infertile men. In these cases all components of the signaling pathway of tryptase were detected as well as expression of COX2. Therefore, our study describes as-yet-unknown interactions between mast cells and fibroblasts, which could be relevant for human fibrotic diseases.

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mentioning

confidence: 99%

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Frungieri

Weidinger

Meineke

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

238

229

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“…In that study, topical application of tranilast (10,30, and 100 mgkg) selectively inhibited collagen deposition in proliferative granulation tissue in a dose-dependent manner without affecting the tissue's content of noncollagen protein (Table 3). Significant reductions in collagen deposition have also been obtained following the oral administration of tranilast (3100 mgkg) in a carrageenin-induced proliferative inflammation model (44) and in a keloid tissue-implant model (47).…”

Section: Effects On Collagen Deposition and Proliferative Disease Modelsmentioning

confidence: 86%

Tranilast: A New Application in the Cardiovascular Field as An Antiproliferative Drug

Isaji

Miyata

Ajisawa

1998

Cardiovascular Drug Reviews

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“…A series of inflammatory cytokines, including interleukin-1, are known to promote inflammation by stimulating the production of various eicosanoids (1). The resulting improvement in circulation, which is based on the modulation of platelets as well as the potent vaso dilator action by prostanoids, is thought to be effective against refractory skin ulcers and arteriosclerosis obliterans (ASO) (2).…”

Section: Short Communicationmentioning

confidence: 99%

Specific Enhancement of Vascular Endothelial Growth Factor (VEGF) Production in Ischemic Region by Alprostadil — Potential Therapeutic Application in Pharmaceutical Regenerative Medicine

et al. 2013

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Abstract. Alprostadil (lipo-PGE1) is a drug delivery system preparation. This preparation is applied to treat refractory skin ulcers and arteriosclerosis obliterans. We investigated the effects of alprostadil by using the earflap ischemic model. The following results were obtained: 1) Treatment with alprostadil significantly increased the VEGF contents in an ischemic ear; 2) Treatment with alprostadil resulted in strongly expressed VEGF levels only in the ischemic region; 3) Image analysis revealed a significant increase in the number of vessel bypasses and paths after flap creation with alprostadil administration compared to the vehicle-treated ears. The results suggest that it may be possible to apply alprostadil as one device for regenerative medical technology.

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Suppressive effects of tranilast on the expression of inducible cyclooxygenase (COX2) in interleukin-1β-stimulated fibroblasts

Cited by 31 publications

References 12 publications

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Tranilast: A New Application in the Cardiovascular Field as An Antiproliferative Drug

Specific Enhancement of Vascular Endothelial Growth Factor (VEGF) Production in Ischemic Region by Alprostadil — Potential Therapeutic Application in Pharmaceutical Regenerative Medicine

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