Tags

Type your tag names separated by a space and hit enter

Propofol Inhibits Lipopolysaccharide-Induced Inflammatory Responses in Spinal Astrocytes via the Toll-Like Receptor 4/MyD88-Dependent Nuclear Factor-κB, Extracellular Signal-Regulated Protein Kinases1/2, and p38 Mitogen-Activated Protein Kinase Pathways.
Anesth Analg. 2015 Jun; 120(6):1361-8.A&A

Abstract

BACKGROUND

In this study, we investigated the effect of propofol, a commonly used IV anesthetic, on lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes and explored the molecular mechanisms by which it occurs.

METHODS

Astrocytes were stimulated with LPS (1.0 μg/mL) in the absence and presence of different concentrations of propofol. The expression of astrocyte marker glial fibrillary acidic protein (GFAP) in astrocytes was detected using immunofluorescence staining and Western blot analysis. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α were measured using an enzyme-linked immunosorbent assay. The mRNA level of Toll-like receptor 4 (TLR4) was determined by semiquantitative reverse transcriptase-polymerase chain reaction. The protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), p- extracellular signal-regulated protein kinases (ERK)1/2, p-c-Jun N-terminal kinase, p-p38 mitogen-activated protein kinase (MAPK), p-I-κBα, I-κBα, and p-nuclear factor-κB (NF-κB)p65 were detected by Western blot.

RESULTS

Our results show that after stimulation with LPS, the levels of IL-1β, IL-6, and tumor necrosis factor-α and the expression of GFAP in astrocytes were up-regulated significantly. In addition, the expression of TLR4, MyD88, p-ERK1/2, p-c-Jun N-terminal kinase, p-p38 MAPK, and p-NF-κBp65 increased, whereas the expression of total I-κBα decreased upon stimulation with LPS. Propofol (10 μM) reduced the secretion of proinflammatory cytokines, inhibited the expressions of GFAP, TLR4, MyD88, p-ERK1/2, p-p38 MAPK, and p-NF-κBp65 in astrocytes challenged with LPS.

CONCLUSIONS

In the present study, propofol 10 μM but not lower clinically relevant or higher supra-clinical concentrations attenuated LPS-induced astrocyte activation and subsequent inflammatory responses by inhibiting the TLR4/MyD88-dependent NF-κB, ERK1/2, and p38 MAPK pathways.

Authors+Show Affiliations

From the *Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, PR China; †Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, PR China; and ‡Department of Anesthetic Pharmacology, Xuzhou Medical College, Xuzhou, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25695672

Citation

Zhou, Cheng-Hua, et al. "Propofol Inhibits Lipopolysaccharide-Induced Inflammatory Responses in Spinal Astrocytes Via the Toll-Like Receptor 4/MyD88-Dependent Nuclear Factor-κB, Extracellular Signal-Regulated Protein Kinases1/2, and P38 Mitogen-Activated Protein Kinase Pathways." Anesthesia and Analgesia, vol. 120, no. 6, 2015, pp. 1361-8.
Zhou CH, Zhu YZ, Zhao PP, et al. Propofol Inhibits Lipopolysaccharide-Induced Inflammatory Responses in Spinal Astrocytes via the Toll-Like Receptor 4/MyD88-Dependent Nuclear Factor-κB, Extracellular Signal-Regulated Protein Kinases1/2, and p38 Mitogen-Activated Protein Kinase Pathways. Anesth Analg. 2015;120(6):1361-8.
Zhou, C. H., Zhu, Y. Z., Zhao, P. P., Xu, C. M., Zhang, M. X., Huang, H., Li, J., Liu, L., & Wu, Y. Q. (2015). Propofol Inhibits Lipopolysaccharide-Induced Inflammatory Responses in Spinal Astrocytes via the Toll-Like Receptor 4/MyD88-Dependent Nuclear Factor-κB, Extracellular Signal-Regulated Protein Kinases1/2, and p38 Mitogen-Activated Protein Kinase Pathways. Anesthesia and Analgesia, 120(6), 1361-8. https://doi.org/10.1213/ANE.0000000000000645
Zhou CH, et al. Propofol Inhibits Lipopolysaccharide-Induced Inflammatory Responses in Spinal Astrocytes Via the Toll-Like Receptor 4/MyD88-Dependent Nuclear Factor-κB, Extracellular Signal-Regulated Protein Kinases1/2, and P38 Mitogen-Activated Protein Kinase Pathways. Anesth Analg. 2015;120(6):1361-8. PubMed PMID: 25695672.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Propofol Inhibits Lipopolysaccharide-Induced Inflammatory Responses in Spinal Astrocytes via the Toll-Like Receptor 4/MyD88-Dependent Nuclear Factor-κB, Extracellular Signal-Regulated Protein Kinases1/2, and p38 Mitogen-Activated Protein Kinase Pathways. AU - Zhou,Cheng-Hua, AU - Zhu,Yang-Zi, AU - Zhao,Pan-Pan, AU - Xu,Chun-Mei, AU - Zhang,Ming-Xing, AU - Huang,He, AU - Li,Jing, AU - Liu,Lu, AU - Wu,Yu-Qing, PY - 2015/2/20/entrez PY - 2015/2/20/pubmed PY - 2015/7/28/medline SP - 1361 EP - 8 JF - Anesthesia and analgesia JO - Anesth. Analg. VL - 120 IS - 6 N2 - BACKGROUND: In this study, we investigated the effect of propofol, a commonly used IV anesthetic, on lipopolysaccharide (LPS)-induced inflammatory responses in astrocytes and explored the molecular mechanisms by which it occurs. METHODS: Astrocytes were stimulated with LPS (1.0 μg/mL) in the absence and presence of different concentrations of propofol. The expression of astrocyte marker glial fibrillary acidic protein (GFAP) in astrocytes was detected using immunofluorescence staining and Western blot analysis. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α were measured using an enzyme-linked immunosorbent assay. The mRNA level of Toll-like receptor 4 (TLR4) was determined by semiquantitative reverse transcriptase-polymerase chain reaction. The protein expressions of TLR4, myeloid differentiation factor 88 (MyD88), p- extracellular signal-regulated protein kinases (ERK)1/2, p-c-Jun N-terminal kinase, p-p38 mitogen-activated protein kinase (MAPK), p-I-κBα, I-κBα, and p-nuclear factor-κB (NF-κB)p65 were detected by Western blot. RESULTS: Our results show that after stimulation with LPS, the levels of IL-1β, IL-6, and tumor necrosis factor-α and the expression of GFAP in astrocytes were up-regulated significantly. In addition, the expression of TLR4, MyD88, p-ERK1/2, p-c-Jun N-terminal kinase, p-p38 MAPK, and p-NF-κBp65 increased, whereas the expression of total I-κBα decreased upon stimulation with LPS. Propofol (10 μM) reduced the secretion of proinflammatory cytokines, inhibited the expressions of GFAP, TLR4, MyD88, p-ERK1/2, p-p38 MAPK, and p-NF-κBp65 in astrocytes challenged with LPS. CONCLUSIONS: In the present study, propofol 10 μM but not lower clinically relevant or higher supra-clinical concentrations attenuated LPS-induced astrocyte activation and subsequent inflammatory responses by inhibiting the TLR4/MyD88-dependent NF-κB, ERK1/2, and p38 MAPK pathways. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/25695672/Propofol_Inhibits_Lipopolysaccharide_Induced_Inflammatory_Responses_in_Spinal_Astrocytes_via_the_Toll_Like_Receptor_4/MyD88_Dependent_Nuclear_Factor_κB_Extracellular_Signal_Regulated_Protein_Kinases1/2_and_p38_Mitogen_Activated_Protein_Kinase_Pathways_ L2 - http://dx.doi.org/10.1213/ANE.0000000000000645 DB - PRIME DP - Unbound Medicine ER -