Expression of human caspase-4 in the gingival epithelium affected with periodontitis: Its involvement in Porphyromonas gingivalis-challenged gingival epithelial cells

Nutthapong Kantrong; Worakanya Buranaphatthana; Doosadee Hormdee; Waraporn Suwannarong; Rajda Chaichit; Komkham Pattanaporn; Poramaporn Klanrit; Suttichai Krisanaprakornkit

doi:10.1016/j.archoralbio.2022.105466

Expression of human caspase-4 in the gingival epithelium affected with periodontitis: Its involvement in Porphyromonas gingivalis-challenged gingival epithelial cells

Arch Oral Biol. 2022 Aug:140:105466. doi: 10.1016/j.archoralbio.2022.105466. Epub 2022 May 24.

Authors

Nutthapong Kantrong¹, Worakanya Buranaphatthana², Doosadee Hormdee³, Waraporn Suwannarong⁴, Rajda Chaichit⁵, Komkham Pattanaporn⁶, Poramaporn Klanrit³, Suttichai Krisanaprakornkit⁷

Affiliations

¹ Department of Restorative Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand; Oral Biology Research Unit, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand; Research Group of Chronic Inflammatory Oral Diseases and Systemic Disease Associated with Oral Health, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
² Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Oral and Maxillofacial Biology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
³ Research Group of Chronic Inflammatory Oral Diseases and Systemic Disease Associated with Oral Health, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand; Department of Oral Biomedical Sciences, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
⁴ Department of Oral Biomedical Sciences, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
⁵ Department of Preventive Dentistry, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
⁶ School of Dentistry, Mae Fah Luang University, Chiang Rai, Thailand.
⁷ Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Oral and Maxillofacial Biology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. Electronic address: suttichai.k@cmu.ac.th.

PMID: 35640321
DOI: 10.1016/j.archoralbio.2022.105466

Abstract

Objective: Implication of human caspase-4 in periodontitis and in sensing periodontal pathogens by gingival epithelial cells (GECs) is unclear. This study aimed to determine caspase-4 and interleukin (IL)-18 expressions in gingival tissues affected with periodontitis and to investigate caspase-4 involvement in mediating innate immune responses in GECs.

Design: Ex vivo, caspase-4 and IL-18 expressions in gingival biopsies, obtained from healthy participants with periodontitis or clinically healthy gingiva (N = 20 each), were determined by immunohistochemistry. In vitro, caspase-4 activation in cultured GECs stimulated with Porphyromonas gingivalis or Fusobacterium nucleatum was analyzed by immunoblotting. mRNA expressions of human β-defensin-2 (hBD-2), IL-8, and IL-18 in stimulated GECs in the presence or absence of a caspase-4 inhibitor were assayed by RT-qPCR.

Results: Ex vivo, compared with healthy gingival epithelium, the epithelium affected with periodontitis displayed a significant decrease in caspase-4 expression (P = 0.015), whereas IL-18 expression was significantly increased (P = 0.012). Moreover, the expression of caspase-4, but not IL-18, was found to be a predictor of periodontitis (P = 0.007). In vitro, caspase-4 was activated in cultured GECs challenged with P. gingivalis, but not F. nucleatum. mRNA upregulations of hBD-2, IL-8, and IL-18 upon P. gingivalis stimulation were significantly reduced when caspase-4 was inhibited (P < 0.05), whereas the inhibitor failed to suppress those inductions by F. nucleatum.

Conclusions: Caspase-4 expression is diminished in the epithelium affected with periodontitis while that of IL-18 is enhanced. Caspase-4 activation in P. gingivalis-infected GECs upregulates the three innate immune effector molecules, suggesting a possible sensing mechanism of caspase-4 in GECs in periodontal disease pathogenesis.

Keywords: Caspase-4; Fusobacterium nucleatum; Gingival epithelium; Innate immunity; Periodontitis; Porphyromonas gingivalis.

MeSH terms

Bacteroidaceae Infections* / enzymology
Bacteroidaceae Infections* / microbiology
Bacteroidaceae Infections* / pathology
Caspases, Initiator* / biosynthesis
Cells, Cultured
Epithelium / enzymology
Epithelium / microbiology
Epithelium / pathology
Gingiva* / enzymology
Gingiva* / microbiology
Gingiva* / pathology
Humans
Interleukin-18 / biosynthesis
Interleukin-8 / biosynthesis
Periodontitis* / enzymology
Periodontitis* / microbiology
Periodontitis* / pathology
Porphyromonas gingivalis* / metabolism
RNA, Messenger / metabolism

Substances

CXCL8 protein, human
IL18 protein, human
Interleukin-18
Interleukin-8
RNA, Messenger
CASP4 protein, human
Caspases, Initiator