Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4
Introduction: The genome of Salmonella enterica serovar Typhimurium contains 13 operons with homology to fimbrial genes. Methods: To investigate the involvement of these fimbrial gene clusters in the expression of cyclooxygenase-2 (COX-2), which is an inducible enzyme involved in the synthesis of pr...
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| Format: | Article |
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Elsevier
2022-08-01
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| Series: | Journal of Microbiology, Immunology and Infection |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1684118221002371 |
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| author | Kei-ichi Uchiya Saki Isono Misa Yoshimura Takeaki Wajima Toshiaki Nikai |
| author_facet | Kei-ichi Uchiya Saki Isono Misa Yoshimura Takeaki Wajima Toshiaki Nikai |
| author_sort | Kei-ichi Uchiya |
| collection | DOAJ |
| description | Introduction: The genome of Salmonella enterica serovar Typhimurium contains 13 operons with homology to fimbrial genes. Methods: To investigate the involvement of these fimbrial gene clusters in the expression of cyclooxygenase-2 (COX-2), which is an inducible enzyme involved in the synthesis of prostanoids, in J774 macrophages infected with S. enterica serovar Typhimurium, we constructed strains carrying a mutation in genes encoding the putative subunit proteins in 12 fimbrial operons. Results: The level of COX-2 expression was lower in macrophages infected with fimA or stcA mutant Salmonella than in those infected with wild-type Salmonella. Therefore, we focused on putative subunit protein StcA and adhesive like protein StcD encoded in the stc operon. Treatment of macrophages with purified recombinant StcD protein, but not StcA, resulted in the activation of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, leading to the expression of not only COX-2 but also of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha. The expression of StcD-induced COX-2 was inhibited by treatment with the Toll-like receptor 4 (TLR4) inhibitor TAK-242, but not by treatment with the lipopolysaccharide (LPS) antagonist polymyxin B. Furthermore, StcD treatment stimulated HEK293 cells expressing TLR4 in the presence of CD14 and MD-2. Conclusion: StcD is a pathogen-associated molecular pattern of S. enterica serovar Typhimurium that is recognized by TLR4 and plays a significant role in the induction of COX-2 expression in macrophages. |
| first_indexed | 2024-04-13T01:28:58Z |
| format | Article |
| id | doaj.art-d1738237f6a84a8d952c8fdb709be8e5 |
| institution | Directory Open Access Journal |
| issn | 1684-1182 |
| language | English |
| last_indexed | 2024-04-13T01:28:58Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Microbiology, Immunology and Infection |
| spelling | doaj.art-d1738237f6a84a8d952c8fdb709be8e52022-12-22T03:08:33ZengElsevierJournal of Microbiology, Immunology and Infection1684-11822022-08-01554581589Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4Kei-ichi Uchiya0Saki Isono1Misa Yoshimura2Takeaki Wajima3Toshiaki Nikai4Corresponding author. Fax: +81 52 834 8090.; Department of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDepartment of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDepartment of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDepartment of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDepartment of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanIntroduction: The genome of Salmonella enterica serovar Typhimurium contains 13 operons with homology to fimbrial genes. Methods: To investigate the involvement of these fimbrial gene clusters in the expression of cyclooxygenase-2 (COX-2), which is an inducible enzyme involved in the synthesis of prostanoids, in J774 macrophages infected with S. enterica serovar Typhimurium, we constructed strains carrying a mutation in genes encoding the putative subunit proteins in 12 fimbrial operons. Results: The level of COX-2 expression was lower in macrophages infected with fimA or stcA mutant Salmonella than in those infected with wild-type Salmonella. Therefore, we focused on putative subunit protein StcA and adhesive like protein StcD encoded in the stc operon. Treatment of macrophages with purified recombinant StcD protein, but not StcA, resulted in the activation of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways, leading to the expression of not only COX-2 but also of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha. The expression of StcD-induced COX-2 was inhibited by treatment with the Toll-like receptor 4 (TLR4) inhibitor TAK-242, but not by treatment with the lipopolysaccharide (LPS) antagonist polymyxin B. Furthermore, StcD treatment stimulated HEK293 cells expressing TLR4 in the presence of CD14 and MD-2. Conclusion: StcD is a pathogen-associated molecular pattern of S. enterica serovar Typhimurium that is recognized by TLR4 and plays a significant role in the induction of COX-2 expression in macrophages.http://www.sciencedirect.com/science/article/pii/S1684118221002371Cyclooxygenase-2FimbriaeSalmonella enterica serovar TyphimuriumStcDToll-like receptor 4 |
| spellingShingle | Kei-ichi Uchiya Saki Isono Misa Yoshimura Takeaki Wajima Toshiaki Nikai Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4 Journal of Microbiology, Immunology and Infection Cyclooxygenase-2 Fimbriae Salmonella enterica serovar Typhimurium StcD Toll-like receptor 4 |
| title | Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4 |
| title_full | Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4 |
| title_fullStr | Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4 |
| title_full_unstemmed | Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4 |
| title_short | Salmonella fimbrial protein StcD induces cyclooxygenase-2 expression via Toll-like receptor 4 |
| title_sort | salmonella fimbrial protein stcd induces cyclooxygenase 2 expression via toll like receptor 4 |
| topic | Cyclooxygenase-2 Fimbriae Salmonella enterica serovar Typhimurium StcD Toll-like receptor 4 |
| url | http://www.sciencedirect.com/science/article/pii/S1684118221002371 |
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