Hydrogen sulfide exposure induces NLRP3 inflammasomedependent IL-1 beta and IL-18 secretion in human mononuclear leukocytes in vitro

• The aim was to investigate if hydrogen sulfide (H2S) induces the formation of the NLRP3 inflammasome and subsequent IL-1 beta and IL-18 secretion in human peripheral blood mononuclear cells (PBMCs) and in the human monocyte cell line THP1. Bacterial production of H2S has been suggested to participate in the inflammatory host response in periodontitis pathogenesis. H2S is a toxic gas with pro-inflammatory properties. It is produced by bacterial degradation of sulfur-containing amino acids, for example, cysteine. We hypothesize that H2S affects the inflammatory host response by inducing formation of the NLRP3 inflammasome and thereby causes the secretion of IL-1 beta and IL-18. PBMCs from eight healthy blood donors, the human monocyte cell line THP1 Null, and two variants of the THP1 cell line unable to form the NLRP3 inflammasome were cultured in the presence or absence of 1 mM sodium hydrosulfide (NaHS) in 24-well plates at 37 degrees C for 24 hr. Supernatants were collected and the IL-1 beta and IL-18 concentrations were measured with DuoSet ELISA Development kit. PBMCs exposed to NaHS produced more IL-1 beta and IL-18 than unexposed control cells (p = .023 and p = .008, respectively). An increase of extracellular potassium ions (K+) inhibited the secretion of IL-1 beta and IL-18 (p = .008). Further, NaHS triggered the secretion of IL-1 beta and IL-18 in human THP1-Null monocytes (p = .0006 and p = .002, respectively), while the NaHS-dependent secretion was reduced in the monocyte cell lines unable to form the NLRP3 inflammasome. Hence, the results suggest that NaHS induces the formation of the NLRP3 inflammasome and thus the secretion of IL-1 beta and IL-18. Enhanced NLRP3 inflammasome-dependent secretion of IL-1 beta and IL-18 in human mononuclear leukocytes exposed to NaHS in vitro is reported. This may be a mode for H2S to contribute to the inflammatory host response and pathogenesis of periodontal disease.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Odontologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dentistry (hsv//eng)

Nyckelord

hydrogen sulfide

IL-1 beta

IL-18

monocytes

NLRP3 inflammasome

periodontitis

ACTIVATION

CELLS

MACROPHAGES

CYTOKINES

DONOR

Dentistry

Oral Surgery & Medicine

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