Cell stress increases XXXX release in @entity5704 inflammasome-mediated @entity8649 , resulting in cytokine imbalance.

@entity1 @entity32 @entity558 @entity5704 @entity1356 @entity1193 @entity8923 @entity1192 @entity8649 @entity829 @entity855
Cell stress is implicated in triggering bouts of systemic @entity32 in @entity1 with @entity8649 . Blood monocytes from @entity1 affected by @entity5704 -mediated @entity829 ( @entity829 ) release greater amounts of @entity1356 than monocytes from unaffected subjects. Here we show that stress lowers the threshold of activation; blood monocytes from @entity829 @entity1 maintain the high levels of secreted @entity1356 (fivefold) and @entity8923 (10-fold) when stimulated with 1,000-fold less @entity558 than that required for full @entity1356 secretion in control subjects. Unexpectedly, @entity1192 secretion is increased 10-fold, indicating that inflammatory episodes in @entity829 may not be entirely a result of @entity1356 but may also involve @entity1192 . In @entity829 monocytes, @entity558 induces the externalization of copious amounts of @entity855 (10-fold), which drive @entity1356 , @entity8923 , and @entity1192 release via activation of the P2X purinoceptor 7. This enhanced @entity855 release appears to be the link between cell stress and increased cytokine secretion in @entity829 . In the later phase after @entity558 stimulation, @entity829 monocytes undergo oxidative stress, which impairs production of the anti-inflammatory @entity1193 ( @entity1193 ). Remarkably, @entity1193 secretion is fully restored by treatment with antioxidants. In two @entity1 with the same @entity5704 mutation, but different disease severity, monocytes from the mildly affected @entity1 exhibited more efficient redox response, lower @entity855 secretion, and more balanced cytokine production. Thus, the robustness of the individual antioxidant response increases the tolerance to stress and reduces the negative effect of the disease. Pharmacologic block of P2X purinoceptor 7 and improved stress tolerance may represent novel treatment strategies in stress-associated inflammatory diseases.
