Blocking Cyclophilins in the Chronic Phase of Asthma Reduces the Persistence of Leukocytes and Disease Reactivation

• DOI: 10.1165/rcmb.2011-0007oc
• Publication Date: 2011-04-15T01:07:49Z
• Authors: Erik J. Stemmy; Molly A. Balsley; Rosalyn A. Jurjus; Jesse M. Damsker; Michael I. Bukrinsky; Stephanie L. Cons...
• Keywords: Proinflammatory cytokine

Allergic asthma is characterized by acute influxes of proinflammatory leukocytes in response to allergen stimulation, followed quiescent (chronic) periods between challenges, during which sustained, low-level inflammation evident. These chronic phases disease are thought be mediated populations persisting within airways and tissues. The lack any situ proliferation these cells, along with their limited lifespan, suggests that a continual recruitment from the circulation needed maintain chronicity. mechanisms regulating this persistent unknown. Although classic leukocyte-attracting chemokines highly elevated after challenge, they return baseline levels 24 hours, remain close undetectable phase. In present study, we investigated whether an alternative family chemoattractants, namely, extracellular cyclophilins, might instead play role persistence asthma, because production known more sustained inflammatory responses. Using new murine model allergic concentrations cyclophilin A, but not chemokines, were indeed detected phase asthma. Furthermore, blocking activity cyclophilins reduced number up 80%. This reduction was also associated significant inhibition reactivation upon subsequent challenge. findings suggest function may provide novel therapeutic strategy for chronicity severity.