Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling
Osteoarthritis (OA) is a deteriorating disease of cartilage tissues mainly characterized as low-grade inflammation of the joint. Innate immune molecule surfactant protein D (SP-D) is a member of collectin family of collagenous Ca2+-dependent defense lectins and plays a vital role in the inflammatory...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.913901/full |
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| author | Huanyu Jiang Huanyu Jiang Yubiao Zhang Yubiao Zhang Geliang Hu Xiaobin Shang Jianghua Ming Ming Deng Yaming Li Yonggang Ma Shiqing Liu Yan Zhou Yan Zhou |
| author_facet | Huanyu Jiang Huanyu Jiang Yubiao Zhang Yubiao Zhang Geliang Hu Xiaobin Shang Jianghua Ming Ming Deng Yaming Li Yonggang Ma Shiqing Liu Yan Zhou Yan Zhou |
| author_sort | Huanyu Jiang |
| collection | DOAJ |
| description | Osteoarthritis (OA) is a deteriorating disease of cartilage tissues mainly characterized as low-grade inflammation of the joint. Innate immune molecule surfactant protein D (SP-D) is a member of collectin family of collagenous Ca2+-dependent defense lectins and plays a vital role in the inflammatory and innate immune responses. The present study investigated the SP-D-mediated innate/inflammatory bioregulation in OA and explored the underlying molecular mechanism. Transcriptome analysis revealed that SP-D regulated genes were strongly enriched in the inflammatory response, immune response, cellular response to lipopolysaccharide (LPS), PI3K-Akt signaling, Toll-like receptor (TLR) signaling, and extracellular matrix (ECM)-receptor interaction pathways. Knockdown of the SP-D gene by the recombinant adeno-associated virus promoted the macrophage specific markers of CD68, F4/80 and TLR4 in the articular cartilage in vivo. SP-D alleviated the infiltration of synovial macrophages and neutrophils, and inhibited TLR4, TNF-α and the phosphorylation of PI3K, Akt and NF-κB p65 in cartilage. SP-D suppressed cartilage degeneration, inflammatory and immune responses in the rat OA model, whilst TAK-242 strengthened this improvement. In in vitro conditions, SP-D pre-treatment inhibited LPS-induced overproduction of inflammation-correlated cytokines such as IL-1β and TNF-α, and suppressed the overexpression of TLR4, MD-2 and NLRP3. SP-D prevented the LPS-induced degradation of ECM by down-regulating MMP-13 and up-regulating collagen II. Blocking of TLR4 by TAK-242 further enhanced these manifestations. We also demonstrated that SP-D binds to the TLR4/MD-2 complex to suppress TLR4-mediated PI3K/Akt and NF-κB signaling activation in chondrocytes. Taken together, these findings indicate that SP-D has chondroprotective properties dependent on TLR4-mediated PI3K/Akt and NF-κB signaling and that SP-D has an optimal bioregulatory effect on the inflammatory and innate responses in OA. |
| first_indexed | 2024-12-11T05:53:12Z |
| format | Article |
| id | doaj.art-d634cbeb733f4c46abf23b20eb4667d9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T05:53:12Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-d634cbeb733f4c46abf23b20eb4667d92022-12-22T01:18:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.913901913901Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 SignalingHuanyu Jiang0Huanyu Jiang1Yubiao Zhang2Yubiao Zhang3Geliang Hu4Xiaobin Shang5Jianghua Ming6Ming Deng7Yaming Li8Yonggang Ma9Shiqing Liu10Yan Zhou11Yan Zhou12Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, ChinaCentral Laboratory, Renmin Hospital of Wuhan University, Wuhan, ChinaOsteoarthritis (OA) is a deteriorating disease of cartilage tissues mainly characterized as low-grade inflammation of the joint. Innate immune molecule surfactant protein D (SP-D) is a member of collectin family of collagenous Ca2+-dependent defense lectins and plays a vital role in the inflammatory and innate immune responses. The present study investigated the SP-D-mediated innate/inflammatory bioregulation in OA and explored the underlying molecular mechanism. Transcriptome analysis revealed that SP-D regulated genes were strongly enriched in the inflammatory response, immune response, cellular response to lipopolysaccharide (LPS), PI3K-Akt signaling, Toll-like receptor (TLR) signaling, and extracellular matrix (ECM)-receptor interaction pathways. Knockdown of the SP-D gene by the recombinant adeno-associated virus promoted the macrophage specific markers of CD68, F4/80 and TLR4 in the articular cartilage in vivo. SP-D alleviated the infiltration of synovial macrophages and neutrophils, and inhibited TLR4, TNF-α and the phosphorylation of PI3K, Akt and NF-κB p65 in cartilage. SP-D suppressed cartilage degeneration, inflammatory and immune responses in the rat OA model, whilst TAK-242 strengthened this improvement. In in vitro conditions, SP-D pre-treatment inhibited LPS-induced overproduction of inflammation-correlated cytokines such as IL-1β and TNF-α, and suppressed the overexpression of TLR4, MD-2 and NLRP3. SP-D prevented the LPS-induced degradation of ECM by down-regulating MMP-13 and up-regulating collagen II. Blocking of TLR4 by TAK-242 further enhanced these manifestations. We also demonstrated that SP-D binds to the TLR4/MD-2 complex to suppress TLR4-mediated PI3K/Akt and NF-κB signaling activation in chondrocytes. Taken together, these findings indicate that SP-D has chondroprotective properties dependent on TLR4-mediated PI3K/Akt and NF-κB signaling and that SP-D has an optimal bioregulatory effect on the inflammatory and innate responses in OA.https://www.frontiersin.org/articles/10.3389/fimmu.2022.913901/fullsurfactant protein Dosteoarthritisinflammationinnate immunitychondrocytetoll-like receptor 4 |
| spellingShingle | Huanyu Jiang Huanyu Jiang Yubiao Zhang Yubiao Zhang Geliang Hu Xiaobin Shang Jianghua Ming Ming Deng Yaming Li Yonggang Ma Shiqing Liu Yan Zhou Yan Zhou Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling Frontiers in Immunology surfactant protein D osteoarthritis inflammation innate immunity chondrocyte toll-like receptor 4 |
| title | Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling |
| title_full | Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling |
| title_fullStr | Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling |
| title_full_unstemmed | Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling |
| title_short | Innate/Inflammatory Bioregulation of Surfactant Protein D Alleviates Rat Osteoarthritis by Inhibiting Toll-Like Receptor 4 Signaling |
| title_sort | innate inflammatory bioregulation of surfactant protein d alleviates rat osteoarthritis by inhibiting toll like receptor 4 signaling |
| topic | surfactant protein D osteoarthritis inflammation innate immunity chondrocyte toll-like receptor 4 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.913901/full |
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