The Role of Caspase-1 and Caspase-4 in Modulating Gingival Epithelial Cell Responses to <i>Aggregatibacter actinomycetemcomitans</i> Infection
Periodontitis is a chronic inflammatory disease characterized by bacterial infection and immune dysregulation. <i>Aggregatibacter actinomycetemcomitans</i> (<i>A. actinomycetemcomitans</i>) is a key pathogen linked to disease progression. Caspase-1 and caspase-4 regulate infl...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Pathogens |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-0817/14/3/295 |
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| Summary: | Periodontitis is a chronic inflammatory disease characterized by bacterial infection and immune dysregulation. <i>Aggregatibacter actinomycetemcomitans</i> (<i>A. actinomycetemcomitans</i>) is a key pathogen linked to disease progression. Caspase-1 and caspase-4 regulate inflammasome activation and cytokine release, yet their roles in gingival epithelial immunity remain unclear. The aim of this study was to elucidate the involvement of caspase-1 and caspase-4 in regulating the immune response to <i>A. actinomycetemcomitans</i> infection in gingival epithelial cells. Human gingival epithelial cells (Ca9-22) and caspase-1- and caspase-4-deficient cells were infected with <i>A. actinomycetemcomitans</i> for 24 h. Inflammatory mediator release was analyzed using Olink proteomics. Bacterial colonization and invasion were assessed using fluorescence-based assays and gentamicin protection assays. Caspase-1- and caspase-4-deficient cells showed significantly altered cytokine and chemokine profiles after infection with <i>A. actinomycetemcomitans,</i> showing reduced IL-17C and IL-18 release. We also found an increased release of TGF-α and LIF from caspase-4-deficient cells, along with elevated levels of the chemokines IL-8, CXCL9, and CXCL10. Additionally, both caspase-1- and caspase-4-deficient cells showed increased bacterial colonization and invasion, particularly in caspase-4-deficient cells. These findings suggest that caspase-1 and caspase-4 play distinct yet essential roles in gingival epithelial immunity, regulating cytokine release, barrier integrity, and defense against <i>A. actinomycetemcomitans</i> colonization. |
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| ISSN: | 2076-0817 |