The Link module of human TSG-6 (Link_TSG6) promotes wound healing, suppresses inflammation and improves glandular function in mouse models of Dry Eye Disease

Oh, Joo Youn; Ryu, Jin Suk; Kim, Hyeon Ji; Kouvatsos, Nikolaos; Dodd, Rebecca J.; Choi, Se Hyun; Kim, Yu Jeong; Milner, Caroline M.; Day, Anthony J.

doi:10.1016/j.jtos.2021.12.012

Cited by 13 publications

(7 citation statements)

References 79 publications

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“…Corneal epithelial defect was observed after corneal vital staining with 3% (v/v) lissamine green dye or 0.25% (v/v) fluorescein dye, and the extent of staining was graded using the standardized scale system (score 0: no staining; score 1: less than one-third; score 2: less than two-thirds; and score 3: more than two-thirds staining of cornea) [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

Lee

Kim

et al. 2023

J Neuroinflammation

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Background Mounting evidence suggests that the immune system plays detrimental or protective roles in nerve injury and repair. Main body Herein we report that both CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells are required to protect corneal nerves against sterile corneal injury. Selective depletion of CD11bhiLy6Ghi or CD11bhiLy6ChiLy6Glo cells resulted in aggravation of corneal nerve loss, which correlated with IL-6 upregulation. IL-6 neutralization preserved corneal nerves while reducing myeloid cell recruitment. IL-6 replenishment exacerbated corneal nerve damage while recruiting more myeloid cells. In mice lacking Toll-like receptor 2 (TLR2), the levels of IL-6 and myeloid cells were decreased and corneal nerve loss attenuated, as compared to wild-type and TLR4 knockout mice. Corneal stromal fibroblasts expressed TLR2 and produced IL-6 in response to TLR2 stimulation. Conclusion Collectively, our data suggest that CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells confer corneal nerve protection under sterile injury by creating a negative-feedback loop to suppress the upstream TLR2–IL-6 axis that drives corneal nerve loss.

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Section: Methodsmentioning

confidence: 99%

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

Lee

Kim

et al. 2023

J Neuroinflammation

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“…However, pre-induction with exogenous TSG-6 promoted the mineralization of DPSCs, even in an in ammatory environment. TSG-6 is composed primarily of two modules, ΔCUB and ΔHA [33]. TSG-6 has multiple functions, including controlling stromal organization and the association of stromal molecules with cell surface receptors and extracellular signaling factors, such as chemokines [34].…”

Section: Discussionmentioning

confidence: 99%

TSG-6 inhibits the NF-κB signaling pathway and promotes the odontogenic differentiation of DPSCs via CD44 in an inflammatory environment

Wang,

Xie,

Xue

et al. 2024

Preprint

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In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

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“…TSG-6 is composed primarily of two modules, ΔCUB and ΔHA [ 37 ]. TSG-6 has multiple functions, including controlling stromal organization and the association of stromal molecules with cell surface receptors and extracellular signaling factors, such as chemokines [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment

Wang,

Xie,

Xue

et al. 2024

Biomolecules

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In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

show abstract

The Link module of human TSG-6 (Link_TSG6) promotes wound healing, suppresses inflammation and improves glandular function in mouse models of Dry Eye Disease

Cited by 13 publications

References 79 publications

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

TSG-6 inhibits the NF-κB signaling pathway and promotes the odontogenic differentiation of DPSCs via CD44 in an inflammatory environment

TSG-6 Inhibits the NF-κB Signaling Pathway and Promotes the Odontogenic Differentiation of Dental Pulp Stem Cells via CD44 in an Inflammatory Environment

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