High impact information on Hsh2d

• Purified T cells from ALX-deficient mice demonstrated increased IL-2 production, CD25 expression, and proliferation in response to TCR/CD28 stimulation [1].
• Negative regulation of interleukin-2 and p38 mitogen-activated protein kinase during T-cell activation by the adaptor ALX [1].
• Consistent with our initial overexpression studies, these data demonstrate that ALX is a negative regulator of T-cell activation [1].
• The phenotype of ALX-deficient mice resembled the phenotype of those deficient in the transmembrane adaptor LAX, and an association between ALX and LAX proteins was demonstrated [1].
• This work assessed whether calphostin C, a new more potent and specific inhibitor of PKC, is also able to restore the activity of Na(+)-K(+)-ATPase in sciatic nerve of ALX-induced diabetic mice and also assessed if continuous administration of H-7 or calphostin C can afford sustained recovery of the ATPase [2].

Biological context of Hsh2d

• 6. Activation of rat ALX inhibited tumor necrosis factor alpha-mediated nuclear factor kappaB activity in a ligand-dependent manner utilizing a luciferase reporter gene system [3].
• These results suggest that anti-inflammatory effects of glucocorticoids depend at least partly on up-regulation of ALX and that the lipoxin system could be a negative feedback regulator for LTB(4) [4].

Anatomical context of Hsh2d

• 1. Lipoxin (LX) A(4) and aspirin-triggered-LX (ATL) are endogenous lipid-derived mediators that regulate leukocyte trafficking via specific LXA(4) receptors (ALX), and are involved in endogenous anti-inflammation and resolution [3].
• To elucidate the interaction of glucocorticoids and lipoxin A(4) for anti-inflammation, we analyzed in vitro expression of lipoxin A(4) receptor (ALX) on human neutrophils and the in vivo anti-inflammatory effect of glucocorticoids and LXA(4) using a dermal inflammation mouse model [4].

Associations of Hsh2d with chemical compounds

• A cross-over study indicated that MDL 29311 did not attenuate the diabetogenic action of ALX, but rather, directly lowered glucose and triglycerides [5].
• The PPI disruptive effect of MK-801 (1 mg/kg) could be reversed by clozapine and ALX 5407, but not by D-serine [6].
• Modulators of the glycine site on NMDA receptors, D-serine and ALX 5407, display similar beneficial effects to clozapine in mouse models of schizophrenia [6].
• ALX mRNA was up-regulated by dexamethasone (Dex) in human neutrophils [4].
• A glucocorticoid receptor antagonist, mifepristone, suppressed up-regulation of ALX induced by Dex [4].

Other interactions of Hsh2d

• These results suggest that ALX, in association with LAX, negatively regulates T-cell activation through inhibition of p38 [1].

References