RGD Reference Report - Absence of PI3Kgamma leads to increased leukocyte apoptosis and diminished severity of experimental autoimmune encephalomyelitis. - Rat Genome Database

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Absence of PI3Kgamma leads to increased leukocyte apoptosis and diminished severity of experimental autoimmune encephalomyelitis.

Authors: Rodrigues, DH  Vilela, MC  Barcelos, LS  Pinho, V  Teixeira, MM  Teixeira, AL 
Citation: Rodrigues DH, etal., J Neuroimmunol. 2010 May;222(1-2):90-4. Epub 2010 Mar 19.
RGD ID: 6482686
Pubmed: PMID:20303183   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jneuroim.2010.02.016   (Journal Full-text)

Phosphatidylinositol-3-kinase gamma (PI3Kgamma) plays an important role in the motility of leukocytes in several models of inflammation. In this work, the role of PI3Kgamma in experimental autoimmune encephalomyelitis (EAE) was investigated. EAE was induced in wild-type and PI3Kgamma deficient mice (PI3Kgamma(-)(/)(-)). WT animals had a peak of clinical symptoms around day 14 post-induction (p.i.). PI3Kgamma(-)(/)(-) animals developed milder EAE signs and peak of disease was noticed only on day 21 p.i. Better clinical outcome correlated with the absence of perivascular cuffs on day 14 p.i. and with decreased levels of CCL2 and CCL5 in brain of PI3Kgamma(-)(/)(-) mice. There was increased leukocyte rolling and adhesion in pial vessels, as assessed by intravital microscopy, at day 14 after EAE induction in WT mice. The latter parameters were unaltered in PI3Kgamma(-)(/)(-) mice subjected to EAE. Moreover, the PI3Kgamma inhibitor AS-605240 given just before the intravital microscopy failed to affect leukocyte rolling or adhesion. Finally, there was a significant increase in the number of apoptotic cells in the CNS of EAE-induced PI3Kgamma(-/-) mice. Our results suggest that PI3Kgamma is involved in EAE and plays a more important role in mediating leukocyte survival than leukocyte adhesion in this experimental model of multiple sclerosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Encephalomyelitis  ISOPik3cg (Mus musculus)6482686; 6482686 RGD 
Experimental Autoimmune Encephalomyelitis  IMP 6482686 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma)

Genes (Mus musculus)
Pik3cg  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)

Genes (Homo sapiens)
PIK3CG  (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma)


Additional Information