Leptin, a 16-kDa protein that is mainly secreted by adipocytes, plays a 
protective role in many cell types. It has been shown that leptin acts in the 
central and peripheral immune system to protect thymocytes. Cytosolic 
phospholipase A(2) (cPLA(2)) is an enzyme that can specifically initiate the 
release of arachidonic acid (AA) to produce eicosanoids, which regulate 
inflammation and immune responses. Our previous work has shown that leptin is 
important to prevent apoptosis of thymocytes. However, the role of cPLA(2) is 
still unclear, and the precise mechanism also remains to be elucidated. In this 
work, we demonstrated that leptin inhibited the LPS-induced toxicity and 
apoptosis of thymocytes. Western blot and RT-PCR showed that leptin led to a 
reduction of cPLA(2) activity and mRNA level, as well as caspase-3 cleavage. 
Moreover, we found that leptin could decrease the activation of p38 MAPK. 
Accordingly, we pre-treated apoptotic thymocytes with the p38 MAPK inhibitor, 
SB203580 and observed an effect similar to the leptin alone treated group. 
SB203580 also suppressed expression of cPLA(2) and cleavage of caspase-3. Based 
on these results, we suggest that leptin could attenuate LPS-induced apoptotic 
injury in mouse thymocyte cells, mainly through the p38/cPLA(2) signalling 
pathway. The study of the regulatory role of leptin in LPS-induced thymocyte 
apoptosis can help to explain the role of leptin in the immune system and may 
provide a novel treatment option in cases of severe trauma, infection, shock, 
organ failure and autoimmune disease caused by thymic atrophy.