Tags

Type your tag names separated by a space and hit enter

Enhanced Ca(2+) response and stimulation of prostaglandin release by the bradykinin B2 receptor in human retinal pigment epithelial cells primed with proinflammatory cytokines.
Biochem Pharmacol. 2015 Sep 15; 97(2):189-202.BP

Abstract

Kallikrein, kininogen and kinin receptors are present in human ocular tissues including the retinal pigment epithelium (RPE), suggesting a possible role of bradykinin (BK) in physiological and/or pathological conditions. To test this hypothesis, kinin receptors expression and function was investigated for the first time in human fetal RPE cells, a model close to native RPE, in both control conditions and after treatment with proinflammatory cytokines. Results showed that BK evoked intracellular Ca(2+) transients in human RPE cells by activating the kinin B2 receptor. Pretreatment of the cells with TNF-α and/or IL-1β enhanced Ca(2+) response in a time- and concentration-dependent additive manner, whereas the potency of BK and that of the selective B2 receptor antagonist, fasitibant chloride, both in the nanomolar range, remained unaffected. Cytokines have no significant effect on cell number and viability and on the activity of other GPCRs such as the kinin B1, acetylcholine, ATP and thrombin receptors. Immunoblot analysis and immunofluorescence studies revealed that cytokines treatment was associated with an increase in both kinin B2 receptor and COX-2 expression and with the secretion of prostaglandin E1 and E2 into the extracellular medium. BK, through activation of the kinin B2 receptor, potentiated the COX-2 mediated prostaglandin release in cytokines-primed RPE cells while new protein synthesis and prostaglandin production contribute to the potentiating effect of cytokines on BK-induced Ca(2+) response. In conclusion, overall data revealed a cross-talk between the kinin B2 receptor and cytokines in human RPE in promoting inflammation, a key feature in retinal pathologies including diabetic retinopathy and macular edema.

Authors+Show Affiliations

Pharmacology Department, Menarini Ricerche SpA, Via Rismondo 12A, 50131 Florence, Italy. Electronic address: rcatalioto@menarini-ricerche.it.Pharmacology Department, Menarini Ricerche SpA, Via Rismondo 12A, 50131 Florence, Italy.Pharmacology Department, Menarini Ricerche SpA, Via Rismondo 12A, 50131 Florence, Italy.Pharmacology Department, Menarini Ricerche SpA, Via Rismondo 12A, 50131 Florence, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26235941

Citation

Catalioto, Rose-Marie, et al. "Enhanced Ca(2+) Response and Stimulation of Prostaglandin Release By the Bradykinin B2 Receptor in Human Retinal Pigment Epithelial Cells Primed With Proinflammatory Cytokines." Biochemical Pharmacology, vol. 97, no. 2, 2015, pp. 189-202.
Catalioto RM, Valenti C, Maggi CA, et al. Enhanced Ca(2+) response and stimulation of prostaglandin release by the bradykinin B2 receptor in human retinal pigment epithelial cells primed with proinflammatory cytokines. Biochem Pharmacol. 2015;97(2):189-202.
Catalioto, R. M., Valenti, C., Maggi, C. A., & Giuliani, S. (2015). Enhanced Ca(2+) response and stimulation of prostaglandin release by the bradykinin B2 receptor in human retinal pigment epithelial cells primed with proinflammatory cytokines. Biochemical Pharmacology, 97(2), 189-202. https://doi.org/10.1016/j.bcp.2015.07.034
Catalioto RM, et al. Enhanced Ca(2+) Response and Stimulation of Prostaglandin Release By the Bradykinin B2 Receptor in Human Retinal Pigment Epithelial Cells Primed With Proinflammatory Cytokines. Biochem Pharmacol. 2015 Sep 15;97(2):189-202. PubMed PMID: 26235941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced Ca(2+) response and stimulation of prostaglandin release by the bradykinin B2 receptor in human retinal pigment epithelial cells primed with proinflammatory cytokines. AU - Catalioto,Rose-Marie, AU - Valenti,Claudio, AU - Maggi,Carlo Alberto, AU - Giuliani,Sandro, Y1 - 2015/07/30/ PY - 2015/06/22/received PY - 2015/07/27/accepted PY - 2015/8/4/entrez PY - 2015/8/4/pubmed PY - 2015/12/15/medline KW - COX-2 KW - Fasitibant chloride KW - Human retinal pigment epithelial cells KW - Intracellular calcium KW - Kinin B(2) receptor KW - Proinflammatory cytokines SP - 189 EP - 202 JF - Biochemical pharmacology JO - Biochem. Pharmacol. VL - 97 IS - 2 N2 - Kallikrein, kininogen and kinin receptors are present in human ocular tissues including the retinal pigment epithelium (RPE), suggesting a possible role of bradykinin (BK) in physiological and/or pathological conditions. To test this hypothesis, kinin receptors expression and function was investigated for the first time in human fetal RPE cells, a model close to native RPE, in both control conditions and after treatment with proinflammatory cytokines. Results showed that BK evoked intracellular Ca(2+) transients in human RPE cells by activating the kinin B2 receptor. Pretreatment of the cells with TNF-α and/or IL-1β enhanced Ca(2+) response in a time- and concentration-dependent additive manner, whereas the potency of BK and that of the selective B2 receptor antagonist, fasitibant chloride, both in the nanomolar range, remained unaffected. Cytokines have no significant effect on cell number and viability and on the activity of other GPCRs such as the kinin B1, acetylcholine, ATP and thrombin receptors. Immunoblot analysis and immunofluorescence studies revealed that cytokines treatment was associated with an increase in both kinin B2 receptor and COX-2 expression and with the secretion of prostaglandin E1 and E2 into the extracellular medium. BK, through activation of the kinin B2 receptor, potentiated the COX-2 mediated prostaglandin release in cytokines-primed RPE cells while new protein synthesis and prostaglandin production contribute to the potentiating effect of cytokines on BK-induced Ca(2+) response. In conclusion, overall data revealed a cross-talk between the kinin B2 receptor and cytokines in human RPE in promoting inflammation, a key feature in retinal pathologies including diabetic retinopathy and macular edema. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/26235941/Enhanced_Ca_2+__response_and_stimulation_of_prostaglandin_release_by_the_bradykinin_B2_receptor_in_human_retinal_pigment_epithelial_cells_primed_with_proinflammatory_cytokines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(15)00423-2 DB - PRIME DP - Unbound Medicine ER -