Effect of pro-inflammatory and immunoregulatory cytokines on human tenocytes.
Tendon injury induces a local inflammatory response, characterized by the induction of pro-inflammatory cytokines. The aim of the present study was to analyze the effects of TNFalpha, IL-6 and IL-10 on key parameters of tendon homeostasis. Cultured primary human tenocytes were treated with the recombinant cytokines IL-6, IL-10, TNFalpha, or combinations of TNFalpha with IL-6 and IL-10 (10 ng/mL, 6, 24 h). Expression of type I collagen, elastin, MMP-1, TNFalpha, IL-1beta, IL-6, IL-10, and suppressors of cytokine signaling (SOCS1, 3) was analyzed with the use of RTD-PCR, immunocytochemistry, and Western blot analysis. In response to TNFalpha, tenocytes reduced their type I collagen deposition but increased their elastin gene expression and highly upregulated their expression for MMP-1, pro-inflammatory (TNFalpha, IL-1beta) and immunoregulatory (IL-6, IL-10) cytokines. TNFalpha stimulation augmented SOCS1, whereas SOCS3 expression in tenocytes was also induced by IL-6. The treatment of tenocytes with IL-6 and IL-10 had no effect on cytokine expression. Neither IL-6 nor IL-10 modulated the observed effects of TNFalpha significantly. These results indicate that TNFalpha strongly activates the tenocytes to amplify their own TNFalpha expression and, subsequently, that of other regulatory cytokines and matrix degrading enzymes. However, the impact of IL-6 and IL-10 on tenocytes remains unclear.
John
Thilo
T
Department for Trauma and Reconstructive Surgery, Charité-Universitätsmedizin, Campus Benjamin Franklin, FEM, Krahmerstr. 6-10, 12207 Berlin, Germany.
Lodka
Dörte
D
Kohl
Benjamin
B
Ertel
Wolfgang
W
Jammrath
Jennifer
J
Conrad
Claudia
C
Stoll
Christiane
C
Busch
Catharina
C
Schulze-Tanzil
Gundula
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D004549:Elastin / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D008875:Middle Aged; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis; D013710:Tendons / Q000166:cytology* / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology*
D024042:Collagen Type I; D053583:Interleukin-1beta; D015850:Interleukin-6; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004549:Elastin; D020781:Matrix Metalloproteinase 1