Bradykinin upregulates IL-8 production in human gingival fibroblasts stimulated by interleukin-1beta and tumor necrosis factor alpha. 2005

Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
Department of Pediatric Dentistry, Institute of Odontology, Karolinska Institutet, Huddinge, Sweden.

The proinflammatory mediator bradykinin (BK) is suggested to play an important role in the pathogenesis of various inflammatory diseases including periodontitis. In this study, BK per se stimulated interleukin-8 (IL-8) production in human gingival fibroblasts in vitro. Furthermore, BK upregulated the stimulatory effect of the cytokines IL-1beta and TNFalpha on the production of IL-8. The stimulatory effect of BK on the IL-1beta- or TNFalpha-stimulated IL-8 production was reduced in the presence of BK B2 receptor antagonist HOE 140, whereas the B1 receptor antagonist Lys-(des-arg9, Leu8)-BK had no effect. Similar to BK, the calcium ionophore A23187 also upregulated the stimulatory effect of IL-1beta and TNFalpha on IL-8 production. The protein kinase C (PKC) inhibitor bisindolylmaleimide, BIS, significantly reduced the stimulatory effect of BK on IL-1beta and TNFalpha increased IL-8 production but did not affect the production of IL-8 stimulated by cytokines alone. The specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 reduced IL-8 production stimulated by the combination of BK and IL-1beta as well as the IL-1beta-stimulated IL-8 production. In conclusion, this study shows that BK upregulates IL-1beta- and TNFalpha-stimulated IL-8 production via BK B2 receptor and that PKC signal pathway seems to be involved in the upregulation of the cytokine-induced IL-8 production in gingival fibroblasts. This stimulatory effect of BK on IL-8 production may contribute to the maintenance of the gingival inflammation and enhanced risk for destruction of gingival connective tissue.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007375 Interleukin-1 A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D007476 Ionophores Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. Ionophore
D007609 Kallidin A decapeptide bradykinin homolog cleaved from kininogen by kallikreins. It is a smooth-muscle stimulant and hypotensive agent that acts by vasodilatation. Lysyl Bradykinin,Kallidin Tetraacetate,Kallidin, (D)-Isomer,Lys-Bradykinin,Lysine Bradykinin,N2-L-Lysylbradykinin,Bradykinin, Lysine,Bradykinin, Lysyl,Lys Bradykinin,N2 L Lysylbradykinin,Tetraacetate, Kallidin
D008301 Maleimides Derivatives of maleimide (the structural formula H2C2(CO)2NH) containing a pyrroledione ring where the hydrogen atom of the NH group is replaced with aliphatic or aromatic groups.
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D001920 Bradykinin A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg,Bradykinin Acetate, (9-D-Arg)-Isomer,Bradykinin Diacetate,Bradykinin Hydrochloride,Bradykinin Triacetate,Bradykinin, (1-D-Arg)-Isomer,Bradykinin, (2-D-Pro)-Isomer,Bradykinin, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (2-D-Pro-7-D-Pro)-Isomer,Bradykinin, (3-D-Pro)-Isomer,Bradykinin, (3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (5-D-Phe)-Isomer,Bradykinin, (5-D-Phe-8-D-Phe)-Isomer,Bradykinin, (6-D-Ser)-Isomer,Bradykinin, (7-D-Pro)-Isomer,Bradykinin, (8-D-Phe)-Isomer,Bradykinin, (9-D-Arg)-Isomer,Arg Pro Pro Gly Phe Ser Pro Phe Arg
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell

Related Publications

Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
November 2004, Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
October 2006, Archives of oral biology,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
January 2004, Journal of the International Academy of Periodontology,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
December 2009, Journal of periodontal research,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
December 2003, Journal of periodontology,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
April 2009, Journal of periodontal research,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
January 1999, Journal of dental research,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
January 1998, Cytokine,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
July 2010, Molecular nutrition & food research,
Gustaf Brunius, and Helena Domeij, and Agneta Gustavsson, and Tülay Yucel-Lindberg
August 2000, Immunopharmacology and immunotoxicology,
Copied contents to your clipboard!