Evidence for an innate immune response in the immature human intestine: Toll-like receptors on fetal enterocytes

被引:148
作者
Fusunyan, RD [1 ]
Nanthakumar, NN [1 ]
Baldeon, ME [1 ]
Walker, WA [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Gastroenterol Lab,Combined Program Pediat Gas, Charlestown, MA 02129 USA
关键词
D O I
10.1203/00006450-200104000-00023
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
The intestinal epithelium is an active participant in the mucosal immune response against luminal pathogens. Microorganisms and their cell wall products, i.e. lipopolysaccharide (LPS), can stimulate the enterocyte to produce an innate immune response with the increased production of IL-8 via an activation of the transcription factor NF kappaB. The innate response mechanism, however, has not been understood until the recent description of a family of human toll-like receptors (hTLR) on immune cells that interact with LPS and modulate the IL-8 response via an intracellular signal transduction pathway similar to that of the IL-1 receptor family. Accordingly, in this study we have sought to determine the constitutive and regulated expression of hTLR on a nonmalignant human fetal primary small intestinal cell line (H4 cells) and on small intestinal samples of ileum from human fetuses (age 18-21 wk). Specimens were examined by reverse-transcription PCR, Western blot analysis, and immunofluorescence for hTLR2 and hTLR4 mRNA and protein and to determine whether their expression was regulated by LPS or by an endogenous inflammatory stimulus, IL-1 beta. hTLR2 and hTLR4 were expressed constitutively on H4 cells and on human fetal small intestinal enterocytes, predominantly on the basolateral surface of crypt enterocytes. Inflammatory stimuli appeared to regulate hTLR transcription (IL-IP increased both hTLR2 and hTLR4 whereas LPS decreased hTLR4) and possibly translation (qualitative observations). The presence of hTLR on human fetal enterocyte suggests a mechanism for the innate immune response to pathogens and could provide the basis for further study of the accentuated inflammatory response in age-dependent gastrointestinal diseases such as necrotizing enterocolitis.
引用
收藏
页码:589 / 593
页数:5
相关论文
共 22 条
  • [1] Toll-like receptors in the induction of the innate immune response
    Aderem, A
    Ulevitch, RJ
    [J]. NATURE, 2000, 406 (6797) : 782 - 787
  • [2] Toll signaling pathways in the innate immune response
    Anderson, KV
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (01) : 13 - 19
  • [3] Bloom P D, 1996, Semin Gastrointest Dis, V7, P151
  • [4] Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing toll-like receptors
    Cario, E
    Rosenberg, IM
    Brandwein, SL
    Beck, PL
    Reinecker, HC
    Podolsky, DK
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (02) : 966 - 972
  • [5] Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction
    Chow, JC
    Young, DW
    Golenbock, DT
    Christ, WJ
    Gusovsky, F
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) : 10689 - 10692
  • [6] Chuang TH, 2000, EUR CYTOKINE NETW, V11, P372
  • [7] ECKKMANN L, 1993, GASTROENTEROLOGY, V105, P1689
  • [8] HROMOCKYJ AE, 1999, INFECTIONS GASTROINT, P603
  • [9] The IκB/NF-κB system:: a key determinant of mucosal inflammation and protection
    Jobin, C
    Sartor, RB
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2000, 278 (03): : C451 - C462
  • [10] The Toll-receptor family and central of innate immunity
    Kopp, EB
    Medzhitov, R
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1999, 11 (01) : 13 - 18