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Interleukin‐1β‐induced Prostaglandin E2 Production in Human Myometrial Cells: Role of a Pertussis Toxin‐sensitive Component
Author(s) -
HERTELENDY FRANK,
RASTOGI PRERNA,
MOLNÁR MIKLÓS,
ROMERO ROBERTO
Publication year - 2001
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.8755-8920.2001.450304.x
Subject(s) - pertussis toxin , mapk/erk pathway , phosphorylation , protein kinase a , signal transduction , kinase , biology , microbiology and biotechnology , prostaglandin e2 , prostaglandin , medicine , endocrinology , g protein , chemistry
PROBLEM: The objective of this study was to evaluate the possible role of pertussis toxin (PTX)‐sensitive G‐protein(s) in interleukin‐1β (IL‐1) signaling in human myometrial cells (HMC).
METHOD: Primary cultures of HMC were stimulated with human recombinant IL‐1 alone or in combination with PTX. Prostaglandin (PG) E2 in the medium was measured by radioimmunoassay, cyclooxygenase type 2 (Cox‐2) and IκB by western analysis, and the activities of two members of the mitogen‐activated protein kinase (MAPK) family of enzymes, ERK‐2 and JNK, by the phosphorylation of appropriate substrates.
RESULTS: IL‐1 increased PGE2 output during an 18‐hr long incubation by 21.7‐fold ( n =5 experiments). This increase was inhibited by 57% after pretreatment overnight with PTX. IL‐1‐induced expression of Cox‐2 protein was also suppressed to a similar degree in PTX‐treated HMC cultures. Degradation of the nuclear factor kappa B (NF‐κB)‐inhibiting protein (IκB), a critical step in IL‐1 signaling to the nucleus, was significantly inhibited by PTX, as was IL‐1‐induced activation of ERK‐2 and JNK.
CONCLUSIONS: It is suggested that the occupied IL‐1 receptor‐generated signal in HMC is transmitted by multiple pathways. One is coupled to a PTX‐sensitive G‐protein upstream from the MAPK phosphorylation cascade. This, in turn, may interact with another signaling pathway, the activation of NF‐κB, via the phosphorylation of the IκB kinase complex.