Effects of Ropivacaine Hydrochloride on the Expression of Type I Interferon and Its Receptor in SH-SY5Y Cells

Main Article Content

Xianjie Wen
Zhaoxia Wu
Weidong Lin
Yiqun Li
Xiaoping Wang


Nerve injury caused by local anesthetics is a hot issue that people pay close attention to, and its mechanism has not been fully clarified. Type I interferon (I-IFN) is an important factor in regulating inflammatory response. In this study, SH-SY5Y cells were injured by ropivacaine hydrochloride in vitro. The cell viability, apoptosis rate, mRNA and protein expression of I-IFN and its receptor IFNAR, as well as the contents of inflammatory cytokines TNF-α, IL-6 and IL-10 were detected to explore the correlation between I-IFN and neurotoxicity induced by ropivacaine hydrochloride. The results showed that after treated with ropivacaine hydrochloride, the cell viability was decreased, the apoptosis rate was increased, the mRNA and protein expressions of IFN-α, IFN-β, IFNAR1 and IFNAR2 were up-regulated, and the contents of inflammatory factors TNF - α, IL-6 and IL-10 were increased. These results suggest that type I interference and its receptor are associated with neurotoxicity of local anesthetics.

Type I interference, inflammatory reaction, ropivacaine hydrochloride, neurotoxicity.

Article Details

How to Cite
Wen, X., Wu, Z., Lin, W., Li, Y., & Wang, X. (2020). Effects of Ropivacaine Hydrochloride on the Expression of Type I Interferon and Its Receptor in SH-SY5Y Cells. Journal of Pharmaceutical Research International, 32(22), 1-10. https://doi.org/10.9734/jpri/2020/v32i2230766
Original Research Article


Gun SY, Claser C, Tan KS, Rénia L. Interferons and interferon regulatory factors in malaria. Mediators Inflamm. 2014;2014:243713.

Capobianchi MR, Uleri E, Caglioti C, Dolei A. Type I IFN family members: similarity, differences and interaction. Cytokine Growth Factor Rev. 2015;26(2):103-111.

Durbin RK, Kotenko SV, Durbin JE. Interferon induction and function at the mucosal surface. Immunol Rev. 2013;255(1):25-39.

De Weerd NA, Nguyen T. The interferons and their receptors--distribution and regulation. Immunol Cell Biol. 2012;90(5):483-491.

Nallar SC, Kalvakolanu DV. Interferons, signal transduction pathways, and the central nervous system. J Interferon Cytokine Res. 2014;34(8):559-576.

Choubey D. Type I interferon (IFN)-inducible Absent in Melanoma 2 proteins in neuroinflammation: implications for Alzheimer's disease. J Neuroinflammation. 2019;16(1):236.

Boyle DL, Soma K, Hodge J, et al. The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis. Ann Rheum Dis. 2015;74(6):1311-1316.

Danziger O, Pupko T, Bacharach E, Ehrlich M. Interleukin-6 and Interferon-α Signaling via JAK1-STAT Differentially Regulate Oncolytic versus Cytoprotective Antiviral States. Front Immunol. 2018;9:94.

Owen KL, Brockwell NK, Parker BS. JAK-STAT Signaling: A double-edged sword of immune regulation and cancer progression. Cancers (Basel). 2019;11(12):2002.

Liu Y, Gibson SA, Benveniste EN, Qin H. Opportunities for translation from the bench: therapeutic intervention of the JAK/STAT pathway in neuroinflammatory diseases. Crit Rev Immunol. 2015;35(6):505-527.

Zhang K, Yang S, Luo C. TNF-alpha and TNF-R1 regulate bupivacaine-induced apoptosis in spinal cord dorsal root ganglion neuron. Eur J Pharmacol. 2018;833:63-68.

Kan H, Wang Y, Wang D, et al. Cordycepin rescues lidocaine-induced neurotoxicity in dorsal root ganglion by interacting with inflammatory signaling pathway MMP3. Eur J Pharmacol. 2018;827:88-93.

Piegeler T, Votta-Velis EG, Bakhshi FR, et al. Endothelial barrier protection by local anesthetics: ropivacaine and lidocaine block tumor necrosis factor-α-induced endothelial cell Src activation. Anesthesiology. 2014;120(6):1414-1428.

Gray A, Marrero-Berrios I, Weinberg J, et al. The effect of local anesthetic on pro-inflammatory macrophage modulation by mesenchymal stromal cells. Int Immunopharmacol. 2016;33:48-54.

Wen X, Li Y, Liu X, et al. Roles of CaMKIIβ in the neurotoxicity induced by ropivacaine hydrochloride in dorsal root ganglion. Artif Cells Nanomed Biotechnol. 2019;47(1):2948-2956. DOI:10.1080/21691401.2019.1642208

Wen X, Liang H, Li H, et al. In vitro neurotoxicity by ropivacaine is reduced by silencing Cav3.3 T-type calcium subunits in neonatal rat sensory neurons. Artif Cells Nanomed Biotechnol. 2018;46(8):1617-1624.

Wen X, Lai X, Li X, Zhang T, Liang H. The effects of ropivacaine hydrochloride on the expression of CaMK II mRNA in the dorsal root ganglion neurons. Biomed Pharmacother. 2016;84:2014-2019.

Chen K, Liu J, Cao X. Regulation of type I interferon signaling in immunity and inflammation: A comprehensive review. J Autoimmun. 2017;83:1-11.

Taylor JM, Minter MR, Newman AG, Zhang M, Adlard PA, Crack PJ. Type-1 interferon signaling mediates neuro-inflammatory events in models of Alzheimer's disease. Neurobiol Aging. 2014;35(5):1012-1023.

Palanivel JA, Macbeth AE, Chetty NC, Levell NJ. An insight into JAK-STAT signalling in dermatology. Clin Exp Dermatol. 2014;39(4):513-518.

Goldmann T, Blank T, Prinz M. Fine-tuning of type I IFN-signaling in microglia--implications for homeostasis, CNS autoimmunity and interferonopathies. Curr Opin Neurobiol. 2016;36:38-42. DOI:10.1016/j.conb.2015.09.003

Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5(5): 375-386.