MOB-1 and TNF-alpha interact to induce microvascular lung injury.

We have recently identified the alpha-chemokine mob-1 as a highly inducible gene in several rat models of microvascular lung injury, whose expression was suppressed by inhibition of tumor necrosis TNF-alpha (TNF-alpha). This work provides further insight into the relationship between mob-1 and TNF-alpha in the development of lung injury assessed by pulmonary edema and leukosequestration. First, pulmonary mob-1 and TNF-alpha were upregulated in animals subjected to lung injury produced by the intratracheal administration of recombinant TNF-alpha and recombinant mob-1, respectively. Second, mob-1 inhibition by intratracheal anti-mob-1 antibody attenuated lung injury induced by recombinant TNF-alpha. Third, pretreatment with anti-TNF-alpha monoclonal antibody administered intratracheally abrogated recombinant mob-1-induced microvascular lung injury. In vitro, mob-1 and TNF-alpha increased each other's production in RAW 264.7 cells and mob-1 or TNF-alpha inhibition prevented endotoxin-induced upregulation of TNF-alpha or mob-1, respectively, from these cells. Together, these data suggest that mob-1 and TNF-alpha interact to promote lung inflammation.