IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway

被引:99
作者
Kaplanski, G
Teysseire, N
Farnarier, C
Kaplanski, S
Lissitzky, JC
Durand, JM
Soubeyrand, J
Dinarello, CA
Bongrand, P
机构
[1] HOP ST MARGUERITE, SERV MED INTERNE, F-13009 MARSEILLE, FRANCE
[2] FAC MED MARSEILLE, UNITE RICKETTSIES, F-13009 MARSEILLE, FRANCE
[3] TUFTS UNIV NEW ENGLAND MED CTR, DEPT MED, DIV GEOG MED & INFECT DIS, BOSTON, MA 02111 USA
关键词
Mediterranean spotted fever; Rickettsia conorii; vasculitis; IL-8; IL-1;
D O I
10.1172/JCI118354
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Mediterranean spotted fever due to infection by Rickettsia conorii, is characterized by a general vasculitis. This vasculitis is thought to be due to a direct injury to endothelial cells induced by R. conorii. However, production and activity of cytokines on endothelial cells is an important pathway in inflammation, and part of the underlying mechanism of vasculitis, In the present studies, human umbilical vein endothelial cells (HUVEC) infected with R. conorii actively secrete high levels of IL-8 and IL-6 (P < 0.002, and P < 0.03, respectively, compared with uninfected cells). IL-1 alpha, IL-1 beta, or TNF alpha were not detected in the culture supernates. Nevertheless, IL-6 and IL-8 production was due, in a large part, to a cell-associated form of IL-1 alpha expressed on R. conorii-infected HUVEC, since production of these cytokines was suppressed by 80% (P = 0.0001) and 85% (P < 0.04) by the addition of IL-1 receptor antagonist, or anti-IL-1 alpha antibodies (60% inhibition, P < 0.01 and 65% inhibition, P < 0.05, respectively) and IL-1 alpha was measured after lysis of R. conorii-infected HUVEC but not in uninfected cells (P < 0.01). Rickettsial lipopolysaccharide does not seem to be involved, since polymyxin B did not reduce cytokine secretion. On the contrary, infection by intracellular R. conorii appears to be necessary to induce IL-1 alpha and subsequently IL-8, since formalin-fixed R. conorii did not induce cytokine production, These observations demonstrate that R. conorii-infected HUVEC secrete IL-6 and IL-8 via the induction of cell-associated IL-1 alpha, providing a possible mechanism for the vasculitis observed in Mediterranean spotted fever.
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页码:2839 / 2844
页数:6
相关论文
共 48 条
  • [1] CELL-CELL ADHESION MEDIATED BY BINDING OF MEMBRANE-ANCHORED TRANSFORMING GROWTH FACTOR-ALPHA TO EPIDERMAL GROWTH-FACTOR RECEPTORS PROMOTES CELL-PROLIFERATION
    ANKLESARIA, P
    TEIXIDO, J
    LAIHO, M
    PIERCE, JH
    GREENBERGER, JS
    MASSAGUE, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (09) : 3289 - 3293
  • [2] BAGGIOLINI M, 1994, ADV IMMUNOL, V55, P97
  • [3] BAKOUCHE O, 1991, J IMMUNOL, V147, P2164
  • [4] THE BIOLOGY OF CACHECTIN/TNF - A PRIMARY MEDIATOR OF THE HOST RESPONSE
    BEUTLER, B
    CERAMI, A
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1989, 7 : 625 - 655
  • [5] INTERLEUKIN-1 (IL-1) INDUCES BIOSYNTHESIS AND CELL-SURFACE EXPRESSION OF PROCOAGULANT ACTIVITY IN HUMAN VASCULAR ENDOTHELIAL-CELLS
    BEVILACQUA, MP
    POBER, JS
    MAJEAU, GR
    COTRAN, RS
    GIMBRONE, MA
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1984, 160 (02) : 618 - 623
  • [6] NEUTROPHIL ACTIVATING FACTOR (NAF) INDUCES POLYMORPHONUCLEAR LEUKOCYTE ADHERENCE TO ENDOTHELIAL-CELLS AND TO SUBENDOTHELIAL MATRIX PROTEINS
    CARVETH, HJ
    BOHNSACK, JF
    MCINTYRE, TM
    BAGGIOLINI, M
    PRESCOTT, SM
    ZIMMERMAN, GA
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 162 (01) : 387 - 393
  • [7] Conor A, 1910, B SOC PATHOL EXOT, V8, P492
  • [8] INTERLEUKIN-1 IS AN AUTOCRINE REGULATOR OF HUMAN ENDOTHELIAL-CELL GROWTH
    COZZOLINO, F
    TORCIA, M
    ALDINUCCI, D
    ZICHE, M
    ALMERIGOGNA, F
    BANI, D
    STERN, DM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (17) : 6487 - 6491
  • [9] DINARELLO CA, 1991, BLOOD, V77, P1627
  • [10] DINARELLO CA, 1987, J IMMUNOL, V139, P1902