Human β-defensin 2 enhances IL-1β production and pyroptosis through P2X7-mediated NLRP3 expression in macrophages

Panpan Wang,Chuanjiang Zhao,Li Gao,Gang Li

doi:10.32604/biocell.2022.016607

Abstract

Periodontal disease is the leading cause of tooth loss, which is also a high-risk factor for other diseases including oral cancer and cardiovascular disease. Periodontitis is one of the most common type of periodontal diseases. Interleukin-1β (IL-1β) plays a key role in the pathogenesis of periodontitis. However, the mechanism how IL-1β is produced during periodontitis is still unclear. In the present study, we found that human β-defensin 2 (hBD2) enhances IL-1β production through an LPS-primed human acute monocytic leukemia (THP-1) macrophage model. Inhibition of P2X purinoceptor 7 (P2X7) reduced hBD2-enhanced IL-1β production. Incubation of LPS-primed THP-1 macrophages with potassium chloride also suppressed hBD2-enhanced IL-1β production. Silence of inflammasome adaptor Nod-like receptor family pyrin domain containing 3 (NLRP3) led to reduced hBD2-enhanced IL-1β production. Likewise, inhibition of caspase-1 also resulted in the decrease of IL-1β. Moreover, an ethidium bromide uptake test indicated that hBD2-activated caspase-1 mediated pyroptotic pore formation. Subsequent lactate dehydrogenase detection and flow cytometric analysis indicated that hBD2 also induced pyroptosis. In brief, these findings illustrated not only the mechanism of hBD2 in enhancing the inflammatory response, but also provided novel therapeutic targets for periodontitis.

Highlights

Periodontitis, affects the gingiva and the supporting connective tissue and alveolar bone, is among the most common human disorders (Williams, 1990)
Results hBD2 treatment enhances IL-1β production in LPS-primed THP-1 macrophages To identify whether hBD2 enhances IL-1β production in periodontitis, the LPS-primed THP-1 macrophage model was used
Results showed that hBD2 promoted mature IL-1β secretion from LPS-primed THP-1 macrophages in a dosedependent way (Fig. 1A)

Summary

Introduction

Periodontitis, affects the gingiva and the supporting connective tissue and alveolar bone, is among the most common human disorders (Williams, 1990). Periodontitis develops with accumulation of dental plaque, disturbances in the oral microbiota, immune response of the host, tissue destruction and ultimate tooth loss (Michaud et al, 2017). Macrophages are amongst the first immune cells respond to bacteria and their products in periodontitis through potently activating caspase-1, producing large amounts of proinflammatory cytokines including interleukin (IL)-1β and IL-18, releasing lactate dehydrogenase (LDH), and. Extracellular stimuli including ATP initiate the assembly of an inflammasome via NOD-like receptors (NLRs, e.g., NLRP3 and AIM2) to activate IL-1β by caspase-1 (Latz, 2010).

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