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Effects of Inactivated Bordetella pertussis on Phosphodiesterase in the Lung of Ovalbumin Sensitized and Challenged Rats

DOI: 10.1155/2014/581738

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Abstract:

This paper indicated that inactivated Bordetella pertussis (iBp) can enhance the lung airway hyperreactivity of the rats sensitized and challenged with OVA. The mechanisms were involved in the upregulation of cAMP-PDE activity and PDE4A, PDE4D, and PDE3 gene expression in the lungs. But only PDE4 activity was different between the OVA and OVA+iBp groups, and PDE4D expression was significantly increased in iBp rats alone. So, our data suggested that cosensitization with OVA and iBp affects lung airway reactivity by modulating the lung cAMP-PDE activity and PDE4D gene expression. 1. Introduction Inactivated Bordetella pertussis (iBp) has been used as a strong Th2 adjuvant to boost allergic responses to antigen such as house dust mite antigen (HDM), ovalbumin (OVA), and ragweed pollen in animal models of asthmatic hypersensitivity from 1968 [1–4]. Systemic administration of iBp enhances these sensitization processes and enhances the pulmonary and systemic immune responses to locally administered HDM [5]. Our experiments have also suggested that simultaneous exposure to OVA and intramuscularly iBp can enhance the bronchial hyperresponsiveness [6]. But how this occurs at the molecular level has not been elucidated. The phosphodiesterase (PDE) superfamily participates in the only cellular pathways for degradation of the ubiquitous intracellular second messengers. It comprises eleven biochemically and pharmacologically distinct enzyme families (PDEs 1-11) that hydrolyze cAMP and/or cGMP [7]. PDE4 is specific for cAMP and comprises four subtypes (A, B, C, and D). It is predominantly expressed and plays an important role in the regulation of cellular functions in inflammatory and immune cells. There has been significant interest in PDE4 inhibitors as a potential therapy for inflammatory diseases such as allergy and asthma [8]. Cyclic adenosine monophosphate (cAMP) relaxes airway smooth muscles in the lung. Our previous study using iBp adjuvants suggested that PDE4 is upregulated in the lung of allergic rats [6]. But whether the adjuvants had effects on PDE activity and expression was unclear. Growing evidence suggests that the D subtype of PDE4-PDE4D plays a key role in balancing relaxation and contraction in airway smooth muscle [9]. The airway smooth muscle contractility of PDE4D-deficient mice is disrupted and no longer responsive to cholinergic stimulation [10]. Interestingly, animals exposed prenatally but not postnatally to cigarette smoke show increased airway hyperresponsiveness after a single intratracheal injection of Aspergillus fumigatus extract.

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