After @entity8 /reperfusion (I/R) injury, monocytes home to the kidney and differentiate into activated macrophages. Whereas proinflammatory macrophages contribute to the @entity8 , an alternatively activated phenotype can promote normal renal repair. The microenvironment of the kidney during the repair phase mediates the transition of macrophage activation from a proinflammatory to a reparative phenotype. In this study, we show that macrophages isolated from @entity19 kidneys during the tubular repair phase after I/R exhibit an alternative activation gene profile that differs from the canonical alternative activation induced by @entity58 -stimulated @entity9094 signaling. This unique activation profile can be reproduced in vitro by stimulation of bone marrow-derived macrophages with conditioned media from serum-starved @entity19 proximal tubule cells. Secreted tubular factors were found to activate macrophage @entity10433 and @entity23117 but not @entity9094 , leading to induction of the unique alternative activation pattern. Using @entity10433 -deficient bone marrow-derived macrophages and pharmacologic inhibition of @entity23117 , we found that tubular cell-mediated macrophage alternative activation is regulated by @entity23117 activation. Both in vitro and after renal I/R, tubular cells expressed @entity2304 , a known @entity23117 activator, and this pathway was required for in vitro alternative activation of macrophages by tubular cells. Furthermore, administration of a neutralizing antibody against @entity2304 after renal I/R attenuated kidney macrophage alternative activation and suppressed tubular proliferation. Taken together, these data show that tubular cells can instruct macrophage activation by secreting @entity2304 , leading to a unique macrophage reparative phenotype that supports tubular proliferation after @entity63 .

@entity2304 Promotes Macrophage Alternative Activation after XXXX /Reperfusion Injury.

@entity2304 :: ('12981(Tax:10090)', 'Gene') :: ['GM-CSF'] @entity8 :: ('MESH:D007674', 'Disease') :: ['kidney ischemia', 'initial kidney damage'] @entity63 :: ('MESH:D007511', 'Disease') :: ['sterile ischemic injury'] @entity19 :: ('10090', 'Species') :: ['mouse', 'murine'] @entity10433 :: ('20848(Tax:10090)', 'Gene') :: ['STAT3'] @entity9094 :: ('20852(Tax:10090)', 'Gene') :: ['STAT6'] @entity58 :: ('16189(Tax:10090)', 'Gene') :: ['IL-4'] @entity23117 :: ('20850(Tax:10090)', 'Gene') :: ['STAT5']
@entity8 :: (MESH:D007674,Disease) :: ['Renal Ischemia']
