A potential role of thymic stromal lymphopoietin in the recruitment of macrophages to mouse intervertebral disc cells via monocyte chemotactic protein 1 induction: Implications for herniated discs

Ohba, Tetsuro; Haro, Hirotaka; Ando, Takashi; Koyama, Kikuhiko; Hatsushika, Kyosuke; Suenaga, Fumiko; Ohnuma, Yuko; Nakamura, Yuki; Katoh, Ryohei; Ogawa, Hideoki; Hamada, Y.; Nakao, Akihiro

doi:10.1002/art.23965

Cited by 31 publications

(40 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15,21 MCP-1 plays a critical role in HD resorption by triggering macrophage infiltration into HD tissue via the PI3K pathway. 19 We have demonstrated gradual decrease of VEGF expression in murine IVD after TNF-a stimulation with aging. 15 In this study, we investigated the age-related reduction in expression of MCP-1 and MMP-3 with or without stimulation with TNF-a and TWEAK and the roles of MCP-1 and MMP-3 in old aged murine IVD tissues.…”

Section: Discussionmentioning

confidence: 72%

See 1 more Smart Citation

Age‐related expression of MCP‐1 and MMP‐3 in mouse intervertebral disc in relation to TWEAK and TNF‐α stimulation

Fujita

Ando

Ohba

et al. 2011

Journal Orthopaedic Research

Self Cite

View full text Add to dashboard Cite

This study was undertaken to investigate the age-related differences of monocyte chemotactic protein-1 (MCP-1) and matrix metalloproteinase-3 (MMP-3) expression in mouse intervertebral disc (IVD) and to determine whether MMP-3 plays a role in disc degeneration. Expression of MCP-1 and MMP-3 mRNA in mouse IVD was assessed by quantitative PCR. The ability of MCP-1 and MMP-3 expression in IVD to respond to TNF-a or TWEAK stimulation was examined by quantitative PCR, WB, ELISA, and immunohistochemistry. IVD derived from MMP-3-deficient and wild-type mice were compared using Safranin-O staining and immunohistochemistry. mRNA levels of MCP-1 and MMP-3 in IVD significantly diminished and the ability of MCP-1 or MMP-3 expression to respond to TNF-a or TWEAK stimulation was significantly reduced as age increased. IVD derived from 64-week-old wild-type mice showed clearly diffuse proteoglycan loss by Safranin-O staining and immunohistochemistry compared with younger mice. However, no loss of proteoglycan and typeII collagen were observed in IVD derived from 64-week-old MMP-3-deficient mice. MCP-1 and MMP-3 expression in mouse IVD showed age-related decreases. The response to inflammation in IVD also displayed age-related changes. Therefore, disc degeneration may vary with the patients' age and targeting MMP-3 may be a possible future therapeutic strategy for disc degeneration. ß

show abstract

Section: Discussionmentioning

confidence: 72%

“…15,19 Briefly, coccygeal IVD tissue specimens were obtained from the mouse tail bone using a dissecting microscope after the skin and soft tissue were removed. For organ culture assays, microscopy was used to harvest coccygeal IVD tissue completely from the end plates.…”

Section: Micementioning

confidence: 99%

Age‐related expression of MCP‐1 and MMP‐3 in mouse intervertebral disc in relation to TWEAK and TNF‐α stimulation

Fujita

Ando

Ohba

et al. 2011

Journal Orthopaedic Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several groups have demonstrated that TSLPR participated in the development of inflammation and tumors [23,24,25]. Signaling followed by an activation of TSLPR by TSLP has been shown to involve phosphatidylinositide 3-kinase (PI3K) and its downstream effector Akt [32,33]. Platelets are also derived from megakaryocytes of hematopoietic cells and are known to be the major players in atherothrombosis pathogenesis [7].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Dong

Lin

Wang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Aims: Thymic stromal lymphopoietin (TSLP) plays an important role in inflammatory diseases and is over-expressed in human atherosclerotic artery specimens. The present study investigated the role of TSLP in platelet activation and thrombosis models in vitro and in vivo, as well as the underlying mechanism and signaling pathway. Methods and Results: Western blotting and flow cytometry demonstrated that the TSLP receptor was expressed on murine platelets. According to flow cytometry, platelet stimulation with TSLP induced platelet degranulation and integrin αIIbβ3 activation. A TSLPR deficiency caused defective platelet aggregation, defective platelet secretion and markedly blunted thrombus growth in perfusion chambers at both low and high shear rates. TSLPR KO mice exhibited defective carotid artery thrombus formation after exposure to FeCl₃. TSLP increased Akt phosphorylation, an effect that was abrogated by the PI3K inhibitors wortmannin and LY294002. The PI3K inhibitors further diminished TSLP-induced platelet activation. TSLP-mediated platelet degranulation, integrin αIIbβ3 activation and Akt phosphorylation were blunted in platelets that lacked the TSLP receptor. Conclusion: This study demonstrated that the functional TSLPR was surface-expressed on murine platelets. The inflammatory cytokine TSLP triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt signaling, which suggests an important role for TSLP in linking vascular inflammation and thrombo-occlusive diseases.

show abstract

“…In the presence of IL-1 and TNFa, TSLP activated mast cells to produce significant levels of proinflammatory cytokines (IL-5, IL-6, IL-13, and GM-CSF) and chemokines (CCL1 and CXCL8), without inducing mast cell degranulation (40). In a recent study, TSLP also induced the macrophage chemotactic protein (MCP)-1 production in intervertebral disc cells, facilitating macrophage recruitment that may be involved in the resorption of herniated disc tissue (41). The current study, besides establishing another cellular target of TSLP, provides evidence for TSLPR-mediated proinflammatory cytokine and chemokines release via STAT3 activation and MAPK phosphorylation in HASM cells.…”

Section: Discussionmentioning

confidence: 98%

Thymic Stromal Lymphopoietin Receptor-Mediated IL-6 and CC/CXC Chemokines Expression in Human Airway Smooth Muscle Cells: Role of MAPKs (ERK1/2, p38, and JNK) and STAT3 Pathways

Shan¹,

Redhu²,

Saleh³

et al. 2010

The Journal of Immunology

110

View full text Add to dashboard Cite

Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as asthma, chronic obstructive pulmonary disease, and atopic dermatitis. Enhanced TSLP expression has been detected in asthmatic airways that correlated with both the expression of Th2-attracting chemokines and with disease severity. Although cumulative evidence suggests that human airway smooth muscle (HASM) cells can initiate or perpetuate the airway inflammation by secreting a variety of inflammatory cell products such as cytokines and chemokines, the role of TSLP in this pathway is not known. In the current study, we sought to investigate whether HASM cells express the TSLP receptor (TSLPR) and whether it is functional. We first demonstrated that primary HASM cells express the transcript and protein of both TSLPR subunits (TSLPR and IL-7Rα). Functionally, TSLPR-mediated HASM activation induced a significant increase in CXC (IL-8/CXCL8), CC (eotaxin-1/CCL11) chemokines, and proinflammatory cytokine IL-6 expression. Furthermore, using biochemical and genetic approaches, we found that TSLP-induced proinflammatory gene expression in HASM involved the transcriptional mechanisms, MAPKs (ERK1/2, p38, and JNK), and STAT3 activation. Finally, TSLPR immunoreactivity in bronchial sections from mild allergic asthmatics suggested the potential in vivo TSLP targeting of HASM. Altogether, our data suggest that the TSLPR-mediated HASM activation induces proinflammatory cytokine and chemokines release that may facilitate inflammatory immune cells recruitment in airways. In addition, it may be inferred that TSLPR is involved in the pathogenesis of allergic asthma through the activation of HASM cells by TSLP.

show abstract

A potential role of thymic stromal lymphopoietin in the recruitment of macrophages to mouse intervertebral disc cells via monocyte chemotactic protein 1 induction: Implications for herniated discs

Cited by 31 publications

References 26 publications

Age‐related expression of MCP‐1 and MMP‐3 in mouse intervertebral disc in relation to TWEAK and TNF‐α stimulation

Age‐related expression of MCP‐1 and MMP‐3 in mouse intervertebral disc in relation to TWEAK and TNF‐α stimulation

Inflammatory Cytokine TSLP Stimulates Platelet Secretion and Potentiates Platelet Aggregation via a TSLPR-Dependent PI3K/Akt Signaling Pathway

Thymic Stromal Lymphopoietin Receptor-Mediated IL-6 and CC/CXC Chemokines Expression in Human Airway Smooth Muscle Cells: Role of MAPKs (ERK1/2, p38, and JNK) and STAT3 Pathways

Contact Info

Product

Resources

About