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Reorientation of prostanoid production accompanies “activation” of adult microglial cells in culture
Author(s) -
Slepko Natalia,
Minghetti Luisa,
Polazzi Elisabetta,
Nicolini Alessia,
Levi Giulio
Publication year - 1997
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19970801)49:3<292::aid-jnr4>3.0.co;2-7
Subject(s) - thromboxane b2 , thromboxane a2 , prostanoid , cyclooxygenase , prostaglandin e2 , thromboxane , prostaglandin , lipopolysaccharide , chemistry , thromboxane a synthase , microglia , prostaglandin h2 , western blot , medicine , endocrinology , microbiology and biotechnology , biology , biochemistry , inflammation , immunology , platelet , receptor , enzyme , gene
Abstract Using morphological, immunocytochemical, and functional parameters we have previously shown that highly purified adult rat microglial cells undergo a process of “activation” when cultured in a serum‐containing medium in the absence of added proinflammatory substances or other factors (Slepko and Levi: Glia 16:241–246, 1996). Here we studied the lipopolysaccharide (LPS)‐evoked production of two prostanoids, thromboxane A 2 (measured as thromboxane B 2 ) (TXB 2 ) and prostaglandin E 2 (PGE 2 ), as a function of microglial “activation.” LPS induced a greater time‐ and dose‐dependent release of TXB 2 , compared to PGE 2 , in the less “activated” cells. Further “activation” led to amplified synthesis of PGE 2 and not of TXB 2 , so that the TXB 2 /PGE 2 ratio changed from 2.2 to 0.25 between the 2nd and 4th day in culture. Western blot experiments showed that the LPS‐evoked expression of the inducible form of cyclooxygenase (COX) was markedly higher in cells exhibiting a more “activated” phenotype. The expression of the constitutive isoform of COX was low in all conditions, was slightly greater in more “activated” cells, and was not affected by LPS. Neither progression in microglial “activation” nor LPS treatment enhanced thromboxane synthase activity. We hypothesize that reorientation of prostanoid synthesis toward a major production of PGE 2 in the more “activated” cells can be largely attributed to an increased inducibility of cellular COX expression, combined with the inability of thromboxane synthase to cope with the increased availability of the COX product prostaglandin H 2 (PGH 2 ), the common precursor of TXA 2 and PGE 2 . In view of the different, and at times opposite, functional activity of TXB 2 and PGE 2 , the described change in prostanoid production pattern may contribute to the role of “activated” microglia in inflammation and host defense. J. Neurosci. Res. 49:292–300, 1997. © 1997 Wiley‐Liss, Inc.