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

Abstract

Asthma is an in ammatory lung disorder characterized by mucus hypersecretion, cellular in ltration, and bronchial hyper-responsiveness. House dust mites (HDM) are the most prevalent cause of allergic sensitization. Canonical and noncanonical in ammasomes are multiprotein complexes that assemble in response to pathogen or danger-associated molecular patterns (PAMPs or DAMPs). Murine caspase-11 engages the noncanonical in ammasome. We addressed the role of caspase-11 in mediating host responses to HDM and subsequent allergic in ammation 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 promotes caspase-11 expression. Additionally, caspase-11 −/− macrophages show reduced release of (KC, IL-6 and IL-12) cytokines, 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 uid (BALF), as well as histological lung tissue showed altered in ammatory responses and reduced neutrophilia in the airways of the caspase-11 −/− mice. These ndings indicate that caspase-11 regulates airway in ammation in response to HDM exposure.

Long-term exposure to house dust mites accelerates lung cancer development in mice

“…HDM is a common indoor aeroallergen associated with the development of asthma [ 14 ] that can induce CLI and lung epithelial damage [ 14 – 17 ]. Thus, we hypothesized that chronic exposure to HDM could accelerate LC development in susceptible hosts through the induction of pro-inflammatory cytokines such as IL-1β [ 18 – 20 ]. At the cellular level, IL-1β is known to stimulate angiogenesis in the tumor microenvironment (TME) [ 21 ], and to induce the production of IL-6 and IL-17A, which are well-established mediators of tumor growth.…”

Regulatory Roles of Flavonoids in Caspase-11 Non-Canonical Inflammasome-Mediated Inflammatory Responses and Diseases

“…Activated caspase-1 subsequently promotes proteolytic maturation and secretion of the pro-inflammatory cytokines interleukin (IL)-1β and -18 through GSDMD pores [ 13 , 14 , 15 , 16 ]. Emerging studies have demonstrated that non-canonical inflammasomes also play critical roles in inflammatory responses and in numerous infectious and inflammatory diseases [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”