PMID- 18975342 OWN - NLM STAT- MEDLINE DCOM- 20090107 LR - 20221207 IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 58 IP - 11 DP - 2008 Nov TI - 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. PG - 3510-9 LID - 10.1002/art.23965 [doi] AB - OBJECTIVE: To determine whether thymic stromal lymphopoietin (TSLP) plays a role in the resorption of herniated disc tissue. METHODS: The expression of TSLP messenger RNA (mRNA) and protein in mouse intervertebral disc cells was assessed by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and immunohistochemical analysis. The ability of mouse intervertebral disc cells to respond to TSLP stimulation was examined by Western blot analysis, ELISA, and protein array analysis. Intracellular signaling pathways involved in TSLP signaling in mouse intervertebral disc cells were investigated using several chemical inhibitors. The role of TSLP in macrophage migration into the intervertebral disc was assessed by in vitro migration assay. Finally, TSLP expression in clinical specimens derived from patients with a herniated disc was examined by immunohistochemistry. RESULTS: Mouse intervertebral disc cells expressed TSLP mRNA and protein upon stimulation with NF-kappaB-activating ligands such as tumor necrosis factor alpha. In addition, the mouse intervertebral disc cells expressed the TSLP receptor and produced monocyte chemotactic protein 1 (MCP-1; CCL2) and macrophage colony-stimulating factor in response to TSLP stimulation. Both anulus fibrosus and nucleus pulposus intervertebral disc cells expressed MCP-1 upon TSLP stimulation, which was mediated via the phosphatidylinositol 3-kinase/Akt pathway. Consistently, the supernatants of TSLP-activated intervertebral disc cultures had the capacity to induce macrophage migration in an MCP-1-dependent manner. Finally, TSLP and MCP-1 were coexpressed in human herniated disc specimens in which macrophage infiltration into the tissue was observed. CONCLUSION: TSLP induced by NF-kappaB-activating ligands in intervertebral discs may contribute to the recruitment of macrophages to the intervertebral disc by stimulating MCP-1 production and may be involved in the resorption of herniated disc tissue. FAU - Ohba, Tetsuro AU - Ohba T AD - University of Yamanashi, Yamanashi, Japan. FAU - Haro, Hirotaka AU - Haro H FAU - Ando, Takashi AU - Ando T FAU - Koyama, Kensuke AU - Koyama K FAU - Hatsushika, Kyosuke AU - Hatsushika K FAU - Suenaga, Fumiko AU - Suenaga F FAU - Ohnuma, Yuko AU - Ohnuma Y FAU - Nakamura, Yuki AU - Nakamura Y FAU - Katoh, Ryohei AU - Katoh R FAU - Ogawa, Hideoki AU - Ogawa H FAU - Hamada, Yoshiki AU - Hamada Y FAU - Nakao, Atsuhito AU - Nakao A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Proteins) RN - 0 (RNA, Messenger) RN - GT0IL38SP4 (Thymic Stromal Lymphopoietin) SB - IM MH - Animals MH - Blotting, Western MH - Bone Resorption/*physiopathology MH - Cell Movement/physiology MH - Cells, Cultured MH - Chemokine CCL2/*metabolism MH - Cytokines/*physiology MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Immunohistochemistry MH - Intervertebral Disc/*cytology/physiology MH - Intervertebral Disc Displacement/*physiopathology MH - Macrophages/*physiology MH - Mice MH - NF-kappa B/physiology MH - Proteins/analysis MH - RNA, Messenger/analysis MH - Reverse Transcriptase Polymerase Chain Reaction MH - Thymic Stromal Lymphopoietin EDAT- 2008/11/01 09:00 MHDA- 2009/01/08 09:00 CRDT- 2008/11/01 09:00 PHST- 2008/11/01 09:00 [pubmed] PHST- 2009/01/08 09:00 [medline] PHST- 2008/11/01 09:00 [entrez] AID - 10.1002/art.23965 [doi] PST - ppublish SO - Arthritis Rheum. 2008 Nov;58(11):3510-9. doi: 10.1002/art.23965.