Receptor Interacting Protein 2 (RIP2) Is Dispensable for OVA-Induced Airway Inflammation in Mice

Abstract

PurposeAsthma is a pulmonary chronic inflammatory disease characterized by airway obstruction and hyperresponsiveness. Pattern recognition receptors are known to play a key role in the development of allergic diseases as well as host defenses against microbial infection. Receptor interacting protein 2 (RIP2), a serine/threonine kinase, is an adaptor molecule of NOD1 and NOD2, and genetic variation in this receptor is known to be associated with the severity of allergic asthma in children. In this study, we examined the role of RIP2 in the development of allergic airway inflammation in a mouse model.MethodsAirway inflammation was induced in mice through intranasal administration of ovalbumin (OVA) after 2 intraperitoneal immunizations with OVA. Lung inflammation and mucus hypersecretion were examined histologically and total cell infiltration in bronchoalveolar (BAL) fluids was determined. Levels of the Th2-related cytokines, IL-5 and IL-13, in lung extracts were measured by ELISA. Serum antigen-specific IgE and IgG1 levels were also assessed.ResultsOVA-induced lung inflammation and mucus hypersecretion were not different between WT and RIP2-deficient mice. The IL-5 and IL-13 levels in the bronchoalveolar (BAL) fluids were also not impaired in RIP2-deficient mice compared to WT mice. Moreover, RIP2 deficiency did not affect serum OVA-specific IgG1 and IgE levels.ConclusionsOur results suggest that RIP2 is not associated with the development of allergic airway inflammation.

Administration of Pigment Epithelium-Derived Factor Inhibits Airway Inflammation and Remodeling in Chronic OVA-Induced Mice via VEGF Suppression

“…The Th2 cytokines IL-4, IL-5, and IL-13 are considered the key molecular mechanisms of asthma and have been shown to be associated with airway inflammation. 20 21 22 23 24 In the present study, the production of Th2 cytokines was significantly increased in OVA-challenged mice. Treatment with PEDF inhibited the levels of Th2 cytokines, such as IL-4, IL-5, and IL-13 in BALF, compared to OVA-challenged mice.…”

Frontline Science: RIP2 promotes house dust mite–induced allergic airway inflammation

“…Indeed, intratracheal delivery of siRNA against RIP2 was shown to improve ova‐induced allergic airway inflammation . However, conflicting reports indicating that RIP2‐deficient mice develop OVA‐induced allergic airway disease to the same extent as wild‐type animals has put the importance of RIP2 in the pathogenesis of such diseases in question . In this study, we examine whether RIP2 is involved in the response to HDM, a more physiologically relevant airway allergen.…”

“…21 However, conflicting reports indicating that RIP2-deficient mice develop OVA-induced allergic airway disease to the same extent as wild-type animals has put the importance of RIP2 in the pathogenesis of such diseases in question. 22 In this study, we examine whether RIP2 is involved in the response to HDM, a more physiologically relevant airway allergen. Following an HDM-induced allergic airway model, RIP2 knockout (KO) mice demonstrated attenuated airway inflammation as well as reduced HDM-specific innate and adaptive responses, suggesting that targeting this kinase may pose some therapeutic benefit in HDM-mediated allergic disease.…”

Allergic asthma: RIPK2 takes the lead

“…7 In contrast, Ripk2 −/− mice on a C57BL/6 background show similar susceptibility to OVA-induced asthma when compared with C57BL/6 WT controls. 8 While differences in genetic background of mice could account for the observed differences in the function of RIPK2 during OVA-induced asthma; Miller et al 6 used HDM-induced asthma as a mouse model system to resolve the role of RIPK2. To induce airway inflammation and asthma, mice are intratracheally sensitized with 60 μ g HDM on day 0 followed by daily HDM challenge (37.5 μ g intratracheally) from days 7 to 11.…”

“…siRNA‐mediated deletion of lung RIPK2 in BALB/c mice during OVA‐induced asthma provide significant protection when compared with wild‐type (WT) BALB/c controls . In contrast, Ripk2 −/− mice on a C57BL/6 background show similar susceptibility to OVA‐induced asthma when compared with C57BL/6 WT controls . While differences in genetic background of mice could account for the observed differences in the function of RIPK2 during OVA‐induced asthma; Miller et al.…”