Caspase-11 regulates lung inflammation in response to house dust mites.

Cellular immunology (2021-11-21)
Arwa Abu Khweek, Marisa R Joldrichsen, Eunsoo Kim, Zayed Attia, Kathrin Krause, Kylene Daily, Shady Estfanous, Kaitlin Hamilton, Asmaa Badr, Midhun N K Anne, Mostafa Eltobgy, Kara N Corps, Cierra Carafice, Xiaoli Zhang, Mikhail A Gavrilin, Prosper N Boyaka, Amal O Amer

Asthma is an inflammatory lung disorder characterized by mucus hypersecretion, cellular infiltration, and bronchial hyper-responsiveness. House dust mites (HDM) are the most prevalent cause of allergic sensitization. Canonical and noncanonical inflammasomes are multiprotein complexes that assemble in response to pathogen or danger-associated molecular patterns (PAMPs or DAMPs). Murine caspase-11 engages the noncanonical inflammasome. We addressed the role of caspase-11 in mediating host responses to HDM and subsequent allergic inflammation using caspase-11-/- mice, which lack caspase-11 while express caspase-1. We found that HDM induce caspase-11 expression in vitro. The presence of IL-4 and IL-13 promote caspase-11 expression. Additionally, caspase-11-/- macrophages show reduced release of IL-6, IL-12, and KC, and express lower levels of costimulatory molecules (e.g., CD40, CD86 and MHCII) in response to HDM stimulation. Notably, HDM sensitization of caspase-11-/- mice resulted in similar levels of IgE responses and hypothermia in response to nasal HDM challenge compared to WT. However, analysis of cell numbers and cytokines in bronchiolar alveolar lavage fluid (BALF) and histopathology of representative lung segments demonstrate altered inflammatory responses and reduced neutrophilia in the airways of the caspase-11-/- mice. These findings indicate that caspase-11 regulates airway inflammation in response to HDM exposure.

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Product Description

Monoclonal Anti-Caspase 11 antibody produced in rat, clone 17D9, purified from hybridoma cell culture