Immunomodulatory effectiveness of azithromycin in prevention of postlaminectomy epidural fibrosis

Emmez, Hakan; Börcek, Alp Özgün; Durdağ, Emre; Uyar, P.; Kaymaz, Memduh; Aykol, Şükrü

doi:10.1179/016164110x12767786356471

Cited by 8 publications

(7 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, the exact mechanisms that underlie the development of epidural fibrosis after laminectomy are still uncertain. It has been found that immune and inflammatory reactions play key roles in the formation of epidural fibrosis [ 33 , 34 ]. After being stimulated by various immune cytokines, fibroblasts tend to proliferate extensively, produce collagen, and release extracellular matrix, which ultimately results in the formation of epidural scar adhesion.…”

Section: Discussionmentioning

confidence: 99%

Local application of rapamycin reduces epidural fibrosis after laminectomy via inhibiting fibroblast proliferation and prompting apoptosis

Sun

Zhao

et al. 2016

J Orthop Surg Res

View full text Add to dashboard Cite

BackgroundEpidural fibrosis is a common complication after laminectomy. It is associated with intractable lower back pain and additional complications. To date, no study has evaluated whether the local application of rapamycin (RAPA) can inhibit fibroblast proliferation and reduce epidural scar adhesion after laminectomy. The results of the present study showed that the local application of RAPA reduces epidural fibrosis after laminectomy in rats.MethodsIn this study, 32 male Sprague-Dawley rats were randomly divided into four groups (0.2 mg/ml RAPA-treated group, 0.1 mg/ml RAPA-treated group, 0.05 mg/ml RAPA-treated group and physiological saline group). Laminectomy was performed at the level of lumbar segment 1 to 2, and different concentrations of RAPA or saline were applied to the laminectomy sites for 10 min. Four weeks after laminectomy, the rats were sacrificed, and the degrees of epidural adhesion in each group were evaluated. Macroscopic assessment, analysis of hydroxyproline content, and histological analysis were used to determine the therapeutic effect of the local application of RAPA on the inhibition of fibroblast proliferation and the reduction of epidural fibrosis after laminectomy. Next, we cultured fibroblasts from epidural scar tissues of rats that had undergone laminectomy. Fibroblasts were exposed to the indicated concentrations of RAPA, and western blotting and TUNEL assays were used to assess the effects of RAPA on inhibiting fibroblasts proliferation and promoting fibroblast apoptosis.ResultsThe results of macroscopic assessments, analysis of hydroxyproline content, and histological analyses indicated that RAPA significantly inhibited fibroblast proliferation and reduced epidural fibrosis in the treated groups in the rat model. The western blotting results indicated that the expression levels of the pro-apoptotic proteins cleaved-PARP and Bax were up-regulated, whereas those of Bcl-2 were reduced. TUNEL assay indicated that the apoptosis rates of fibroblasts were significantly increased after exposure to the indicated concentrations of RAPA.ConclusionsThe local application of RAPA reduced epidural fibrosis after laminectomy by inhibiting the proliferation of fibroblasts, stimulating their apoptosis, and decreasing collagen synthesis. This protocol may be used in new clinical treatment strategies to reduce epidural fibrosis after laminectomy.

show abstract

Section: Discussionmentioning

confidence: 99%

Local application of rapamycin reduces epidural fibrosis after laminectomy via inhibiting fibroblast proliferation and prompting apoptosis

Sun

Zhao

et al. 2016

J Orthop Surg Res

View full text Add to dashboard Cite

show abstract

“…Local immune response is considered critical for each type of post‐operative skeletal fibrosis and some immunosuppressant drugs used to prevent post‐operative skeletal fibrosis have achieved success, including rapamycin, tacrolimus, pimercrolimus, azithromycin, methotrexate and cyclosporin A . Results showed that they could prevent post‐operative skeletal fibrosis by inhibiting fibroblast proliferation, suppressing interleukin 2 (IL‐2) and TGF‐β1 expression, regulating miR‐429 and RhoE expression and activating autophagy and the ER stress signaling pathway …”

Section: Current Therapies For Post‐operative Skeletal Fibrosismentioning

confidence: 99%

Prospective application of stem cells to prevent post‐operative skeletal fibrosis

Song²,

Yan

et al. 2019

Journal Orthopaedic Research

View full text Add to dashboard Cite

Post‐operative skeletal fibrosis is considered one of the major complications causing dysfunction of the skeletal system and compromising the outcomes of clinical treatment. Limited success has been achieved using current therapies; more effective therapies to reduce post‐operative skeletal fibrosis are needed. Stem cells possess the ability to repair and regenerate damaged tissue. Numerous studies show that stem cells serve as a promising therapeutic approach for fibrotic diseases in tissues other than the skeletal system by inhibiting the inflammatory response and secreting favorable cytokines through activating specific signaling pathways, acting as so‐called medicinal signaling cells. In this review, current therapies are summarized for post‐operative skeletal fibrosis. Given that stem cells are used as a promising therapeutic approach for fibrotic diseases, little effort has been undertaken to use stem cells to prevent post‐operative skeletal fibrosis. This review aims at providing useful information for the potential application of stem cells in preventing post‐operative skeletal fibrosis in the near future. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1236–1245, 2019.

show abstract

“…It has been well established that epidural fibrosis formation is a complex multi‐step process associated with a significant reduction in the tissue cellularity and excessive deposition of collagen, fibronectin and dermatan sulphate (DS) . Accumulated evidence has shown that specific cytokines like interleukin (IL)‐2, transforming growth factor (TGF)‐ β and IL‐4 significantly promote the progression of fibrogenesis . In the fibrotic process, fibroblasts are activated by these cytokines, produce multiple collagens and form permanent fibrotic scars …”

Section: Introductionmentioning

confidence: 99%

CCN2 and CCN5 exerts opposing effect on fibroblast proliferation and transdifferentiation induced by TGF‐β

Liu

et al. 2015

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Epidural fibrosis might occur after lumbar discectomy and contributes to failed back syndrome. Transforming growth factor (TGF)-β has been reported to influence multiple organ fibrosis, in which connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed 2 (CCN2) and CCN5 are involved. However, the effect of CCN2 and CCN5 on TGF-β induced fibrosis has not yet been elucidated. This study reports that CCN2 and CCN5 play opposing roles in cell proliferation and transdifferentiation of human skin fibroblasts or rabbit epidural scar-derived fibroblasts exposed to TGF-β. We observed that TGF-β1 induced fibroblasts proliferation and differentiation in a dose-dependent manner (from 0 μg/L to 20 μg/L). Meanwhile, CCN2 expression is up-regulated while CCN5 expression is inhibited by TGF-β1 exposure. Furthermore, it is demonstrated that CCN2 overexpression leads to promoted proliferation and elevated collagen and α-smooth muscle actin (α-SMA) expression, which are inhibited by CCN5 overexpression. Moreover, it is shown that the cysteine knot (CT) domain, present in CCN2 but absent in CCN5, plays an essential part in fibroblast proliferation and differentiation. Additionally, enhanced TGF-β and CCN2 expression but decreased CCN5 expression is found in rabbit epidural scar-derived fibroblasts. Overall, the results show the opposing effects of CCN2 and CCN5 on fibroblast proliferation and transdifferentiation induced by TGF-β.

show abstract

Immunomodulatory effectiveness of azithromycin in prevention of postlaminectomy epidural fibrosis

Cited by 8 publications

References 31 publications

Local application of rapamycin reduces epidural fibrosis after laminectomy via inhibiting fibroblast proliferation and prompting apoptosis

Local application of rapamycin reduces epidural fibrosis after laminectomy via inhibiting fibroblast proliferation and prompting apoptosis

Prospective application of stem cells to prevent post‐operative skeletal fibrosis

CCN2 and CCN5 exerts opposing effect on fibroblast proliferation and transdifferentiation induced by TGF‐β

Contact Info

Product

Resources

About