Bradykinin induces a rapid cyclooxygenase-2 mRNA expression via Ca2+mobilization in human gingival fibroblasts primed with interleukin-1 β

Nakao, Sumi; Ogata, Yorimasa; Modéer, Thomas; Segawa, Masaomi; Furuyama, Shunsuke; Saito, Hiroshi

doi:10.1054/ceca.2001.0206

Cited by 19 publications

(19 citation statements)

References 47 publications

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“…Corroborating with previous data showing a potentiation of [Ca 2+ ]i by BK in human gingival fibroblasts primed with IL-1b, (Nakao et al, 2001), we observed a higher calcium transient amplitude in response to BK when the human gingival fibroblasts were pretreated with IL-1b for 24 h. This response was markedly inhibited when the cells were co-treated with IL-4 together with IL-1b. We have previously shown that BK, but not DALBK, induces a transient increase in [Ca 2+ ]i in human gingival fibroblasts (Lerner et al, 1992), which is most likely due to the fact that the B1 receptor is not constitutively expressed at the same levels as the B2 receptor.…”

Section: Discussionsupporting

confidence: 91%

IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B₁ and B₂ receptors through a STAT6‐dependent mechanism

Souza

Brechter

Reis

et al. 2013

British J Pharmacology

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Background and PurposeBone resorption induced by interleukin‐1β (IL‐1β) and tumour necrosis factor (TNF‐α) is synergistically potentiated by kinins, partially due to enhanced kinin receptor expression. Inflammation‐induced bone resorption can be impaired by IL‐4 and IL‐13. The aim was to investigate if expression of B1 and B2 kinin receptors can be affected by IL‐4 and IL‐13.Experimental ApproachWe examined effects in a human osteoblastic cell line (MG‐63), primary human gingival fibroblasts and mouse bones by IL‐4 and IL‐13 on mRNA and protein expression of the B1 and B2 kinin receptors. We also examined the role of STAT6 by RNA interference and using Stat6‐/‐ mice.Key ResultsIL‐4 and IL‐13 decreased the mRNA expression of B1 and B2 kinin receptors induced by either IL‐1β or TNF‐α in MG‐63 cells, intact mouse calvarial bones or primary human gingival fibroblasts. The burst of intracellular calcium induced by either bradykinin (B2 agonist) or des‐Arg10‐Lys‐bradykinin (B1 agonist) in gingival fibroblasts pretreated with IL‐1β was impaired by IL‐4. Similarly, the increased binding of B1 and B2 ligands induced by IL‐1β was decreased by IL‐4. In calvarial bones from Stat6‐deficient mice, and in fibroblasts in which STAT6 was knocked down by siRNA, the effect of IL‐4 was decreased.Conclusions and ImplicationsThese data show, for the first time, that IL‐4 and IL‐13 decrease kinin receptors in a STAT6‐dependent mechanism, which can be one important mechanism by which these cytokines exert their anti‐inflammatory effects and impair bone resorption.

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Section: Discussionsupporting

confidence: 91%

IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B₁ and B₂ receptors through a STAT6‐dependent mechanism

Souza

Brechter

Reis

et al. 2013

British J Pharmacology

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“…26 Bradykinin, via a B2-dependent mechanism, increased COX-2 protein expression that was enzymatically active as it metabolized endogenous arachidonic acid to PGE 2 . Bradykinin also induced COX-2 expression in human airways and pulmonary artery smooth muscle cells 27,28 and potentiated COX-2 mRNA accumulation in fibroblasts, 29 human endothelial cells, 30 and leptomeninges. 31 It is important to note that, although the in vivo expression of COX-2 in the cTAL has been well described, the present study also demonstrates the expression of COX-2 in mTAL cells in vivo.…”

Section: Discussionmentioning

confidence: 89%

Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

et al. 2004

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Abstract-Cyclooxygenase-2 (COX-2) is constitutively expressed in a subset of thick ascending limb cells in the cortex and medulla and increases when the renin-angiotensin and kallikrein-kinin systems are activated. Although the contribution of angiotensin II to the regulation of COX-2 is known, the effects of bradykinin on COX-2 expression have not been determined in this nephron segment. We evaluated expression of B2 bradykinin receptors in thick ascending limb cells containing COX-2 and the effect of bradykinin on COX-2 expression in primary cultured medullary thick ascending cells. The presence of B2 receptors was studied in renal sections by immunohistochemistry with antibodies against B2, COX-2, and Tamm-Horsfall glycoprotein. B2 receptors were detected on the apical and basolateral portion of the thick ascending cells. These cells also contained COX-2, suggesting that COX-2 expression may be regulated via B2 receptor. Incubation of cultured medullary thick ascending cells with bradykinin (10 Ϫ7 to 10 Ϫ5 mol/L) induced a significant increase on COX-2 protein expression. Maximal expression of COX-2 was observed 4 hours after exposure to bradykinin (10 Ϫ7 mol/L), effect abolished by a B2 receptor antagonist (HOE-140; 10 Ϫ6 mol/L). Prostaglandin E 2 production increased when these cells were challenged with bradykinin for 4 hours, indicating that COX-2 was enzymatically active. We have demonstrated (1) the presence of B2 receptors in thick ascending limb cells expressing COX-2 and (2) the stimulatory effect of bradykinin on COX-2 protein expression, via B2 receptors, in cultured medullary thick ascending cells. We suggest that bradykinin can affect ion transport in the thick ascending limb via a COX-2-mediated mechanism. Key Words: cyclooxygenase Ⅲ bradykinin Ⅲ immunohistochemistry Ⅲ rats Ⅲ kidney Ⅲ receptors, bradykinin Ⅲ prostaglandins P rostaglandins participate in the regulation of the renal circulation 1 and tubular ion transport as well as renin secretion, the latter via a cyclooxygenase-2 (COX-2)-dependent mechanism. 2,3 The constitutive enzyme cyclooxygenase-1 (COX-1) has been identified in the collecting tubules and the renal vasculature. 4,5 Immunohistochemical localization studies have detected COX-2 in the perimacula densa region and a subset of thick ascending limb (TAL) epithelial cells located in the cortex (cTAL) 6,7 and outer medulla (mTAL) 7 as well as in interstitial medullary cells. 8 COX-2 expression in the kidney under basal conditions suggests that COX-2 may have a physiological role. Expression of the COX-2 isoform is increased in the kidney during development, 9,10 adrenalectomy, 11,12 and low-salt diet 13 ; it is decreased by glucocorticoids. 11,12 The kallikrein-kinin system (KKS) 14 contributes to the regulation of renal blood flow and salt and water excretion. The renal effects of bradykinin under physiological conditions are mediated by the B2 receptor, whereas the B1 receptor is expressed in pathological states such as inflammation. 15 Activation of the renin-angiotensin and KKS ...

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“…20,22,23,38 The increased expression of COX-2 in fibroblasts results in enhanced synthesis of PGE 2 . 23,36,37,38 The same phenomenon can be observed in endothelial cells upon induction with IL-α.…”

Section: Discussionmentioning

confidence: 99%

Expression of COX-1 and COX-2 in a Clinical Model of Acute Inflammation

Khan

Iadarola

Yang

et al. 2007

The Journal of Pain

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Cyclooxygenase (COX) plays an important role in the induction of pain and inflammation as well as the analgesic actions of NSAIDs and coxibs. This study evaluates the expression of the two isoforms COX-1 and COX-2 in a clinical model in which the surgical removal of impacted third molars is used to evaluate the analgesic activity of anti-inflammatory drugs. A 3 mm punch biopsy was performed on the oral mucosa overlying one impacted third molar immediately before extraction of two impacted lower third molars. After the second tooth was extracted, a second biopsy was performed adjacent to the surgical site either immediately after surgery, 30, 60 or 120 minutes after surgery. RNA was extracted from the biopsies and RT-PCR was performed to assess mRNA levels of COX-1, COX-2 and glyceraldehyde-3-phosphate dehydrogenase (G3PDH). The RT-PCR products in the biopsies were normalized to G3PDH and compared to baseline. COX-2 mRNA was progressively increased at 30, 60, and 120 minutes after surgery (P<0.05); COX-1 mRNA was transiently decreased at 60 minutes during the post-surgical period (P<0.05). The results demonstrate peripheral elevation of COX-2 following tissue injury, which may contribute to increased prostaglandin E 2 at the site of injury, pain onset and the analgesic activity of both non-selective NSAIDs and selective COX-2 inhibitors.Perspective-This clinical study uses a physiologically relevant model to determine the time course of expression of COX -1 and -2 in acute inflammation of the human oral mucosa. This study furthers our understanding of the contribution of the COX isoforms to acute pain.

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Bradykinin induces a rapid cyclooxygenase-2 mRNA expression via Ca2+mobilization in human gingival fibroblasts primed with interleukin-1 β

Cited by 19 publications

References 47 publications

IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B₁ and B₂ receptors through a STAT6‐dependent mechanism

IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B₁ and B₂ receptors through a STAT6‐dependent mechanism

Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

Expression of COX-1 and COX-2 in a Clinical Model of Acute Inflammation

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Bradykinin induces a rapid cyclooxygenase-2 mRNA expression via Ca2+mobilization in human gingival fibroblasts primed with interleukin-1 β

Cited by 19 publications

References 47 publications

IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B1 and B2 receptors through a STAT6‐dependent mechanism

IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B1 and B2 receptors through a STAT6‐dependent mechanism

Bradykinin Regulates Cyclooxygenase-2 in Rat Renal Thick Ascending Limb Cells

Expression of COX-1 and COX-2 in a Clinical Model of Acute Inflammation

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IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B₁ and B₂ receptors through a STAT6‐dependent mechanism

IL‐4 and IL‐13 inhibit IL‐1β and TNF‐α induced kinin B₁ and B₂ receptors through a STAT6‐dependent mechanism