The gene encoding 5 LO appears to be subject to hor monal regulation, and its neuronal expression is remarkably upregulated during aging, while the glu cocorticoid dexamethasone inhibits 5 LO and LTA4 H mRNA expression in cerebral cortex of asthmatic Enzalutamide rats. Our previous study showed that, in addition to changes in Th1Th2 cytokine ratios, there are also cor responding changes in LTB4 levels, expression of 5 LO, and LTA4 H mRNA in cerebral cortex and lung tissue Inhibitors,Modulators,Libraries in antigen challenged asthmatic rats. In this study, we found that antigen challenge induced an increase in LTB4 content in cerebral cortex and lung tis sue in sensitized guinea pigs, which is consistent with what we previously observed in asthmatic rats.
In addition, we further explored the effect of increased LTB4 in brain on the regulation of airway inflammation and pulmonary function in asthmatic guinea Inhibitors,Modulators,Libraries pigs in this study. We found that LTB4 at Inhibitors,Modulators,Libraries 30 ng via i. c. v. attenuated antigen induced airway contraction and inflammatory cell infiltration in lung tissue. U75302, a BLT1 receptor antagonist, at 100 ng via i. c. v. completely blocked the inhibitory effect of LTB4 on antigen induced lung inflammation and the consequent decrease in pulmon ary function. Additionally, we explored the possible mechanism for the inhibitory effect of i. c. v. LTB4 on inflammation and decreased pulmonary function induced by antigen in this study. We measured plasma levels of ACTH and CORT, and observed that ACTH and CORT levels in plasma increased after antigen chal lenge, which supports the idea that acute stress stimula tion of the HPA axis is involved.
Our postulation is that antigen attack provokes an acute airway response in established disease states, which may Inhibitors,Modulators,Libraries act as an acute stressor to activate the NEI system and regulate the HPA axis response. Inhibitors,Modulators,Libraries We did not find significant differences in airway inflammation and lung mechanical function in sensitized guinea pigs treated inhibitor Baricitinib with U75302 alone via i. c. v. which may suggest that endogenous intracerebral LTB4 activity does not normally play a large role in modulating airway inflammation in this model. Notably, we observed a mild decrease in ACTH and CORT levels in plasma after U75302 block of the endogenous LTB4 receptor. We postulate that the increased endo genous LTB4 induced by antigen challenge may mildly activate the HPA axis, but that this activation of the HPA axis may be not enough to antagonize peripheral inflammation in this asthmatic model. Another possible explanation is that the functional effect of increased endogenous LTB4 induced by antigen challenge may be balanced by other mediators or cytokines in brain. For example, levels of TNF a, IL 1 and IL 6 during asth matic attack in brain are also changed after antigen challenge.