Unmasking of LPA1 receptor-mediated migration response to lysophosphatidic acid by interleukin-1beta-induced attenuation of Rho signaling pathways in rat astrocytes.

Authors: Sato, K  Horiuchi, Y  Jin, Y  Malchinkhuu, E  Komachi, M  Kondo, T  Okajima, F 
Citation: Sato K, etal., J Neurochem. 2011 Apr;117(1):164-74. doi: 10.1111/j.1471-4159.2011.07188.x. Epub 2011 Feb 9.
Pubmed: (View Article at PubMed) PMID:21244430
DOI: Full-text: DOI:10.1111/j.1471-4159.2011.07188.x

Action mechanism of lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), and lysophosphatidic acid (LPA) to regulate motility, an important process of astrogliosis, was investigated in rat astrocytes. While LPA exerted no significant effect on the cell migration, the prior treatment of the cells with LPS or IL-1beta resulted in the appearance of migration activity in response to LPA. The LPS induction of the migration response to LPA was associated with the production of IL-1beta precursor protein and inhibited by the IL-1 receptor antagonist. The IL-1beta treatment also allowed LPA to activate Rac1. The LPA-induced Rac1 activation and migration were inhibited by pertussis toxin, a small interfering RNA specific to LPA(1) receptors, and LPA(1) receptor antagonists, including Ki16425. However, the IL-1beta treatment had no appreciable effect on LPA(1) receptor mRNA expression and LPA-induced activation of ERK, Akt, and proliferation. The induction of the migration response to LPA by IL-1beta was inhibited by a constitutively active RhoA. Moreover, LPA significantly activated RhoA through the LPA(1) receptor in the control cells but not in the IL-1beta-treated cells. These results suggest that IL-1beta inhibits the LPA(1) receptor-mediated Rho signaling through the IL-1 receptor, thereby disclosing the LPA(1) receptor-mediated G(i) protein/Rac/migration pathway.

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CRRD ID: 7174692
Created: 2012-11-15
Species: All species
Last Modified: 2012-11-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.