Protective effect of lithium chloride on pulmonary injury caused by Actinobacillus pleuropneumoniae via inhibition of GSK-3β-NF-κB-dependent pathway

Journal title

Polish Journal of Veterinary Sciences




vol. 25


No 1


Zhang, Y. : College of Veterinary Medicine, Hunan Agricultural University, Furong District, Nongda Road, No.1, Changsha 410128, China ; Xu, W. : College of Veterinary Medicine, Hunan Agricultural University, Furong District, Nongda Road, No.1, Changsha 410128, China ; Tang, Y. : College of Veterinary Medicine, Hunan Agricultural University, Furong District, Nongda Road, No.1, Changsha 410128, China ; Huang, F. : College of Veterinary Medicine, Hunan Agricultural University, Furong District, Nongda Road, No.1, Changsha 410128, China ; Huang, F. : Hunan Engineering Technology Research Center for Veterinary Drugs, Hunan Agricultural University, Furong District, Nongda Road, No.1, Changsha 410128, China



porcine contagious pleuropneumonia ; mouse model ; lithium chloride ; toll-likereceptor 4 ; GSK-3β-NF-κB-dependent pathways

Divisions of PAS

Nauki Biologiczne i Rolnicze




Polish Academy of Sciences Committee of Veterinary Sciences ; University of Warmia and Mazury in Olsztyn


Benga L, Hoeltig D, Rehm T, Rothkoetter HJ, Pabst R, Valentin- -Weigand P; FUGATO-consortium IRAS (2009) Expression levels of immune markers in Actinobacillus pleuropneumoniae infected pigs and their relation to breed and clinical symptoms. BMC Vet Res 5: 13.
Boren J, Shryock G, Fergis A, Jeffers A, Owens S, Qin W, Koenig KB, Tsukasaki Y, Komatsu S, Ikebe M, Idell S, Tucker TA (2017) Inhibition of glycogen synthase kinase 3β blocks mesomesenchymal transition and attenuates streptococcus pneumonia-mediated pleural injury in mice. Am J Pathol 187: 2461-2472.
Brogaard L, Klitgaard K, Heegaard PM, Hansen MS, Jensen TK, Skovgaard K (2015) Concurrent host-pathogen gene expression in the lungs of pigs challenged with Actinobacillus pleuropneumoniae. BMC Genomics 16: 417.
Chang Y, Chen C, Lin C, Lu S, Cheng M, Kuo C, Lin Y (2013) Regulatory role of GSK-3β on NF-κB, nitric oxide, and TNF-α in Group A Streptococcal infection. Mediators Inflamm 2013: 720689.
Chen K, Wu Y, Zhu M, Deng Q, Nie X, Li M, Wu M, Huang X (2013) Lithium chloride promotes host resistance against Pseudomonas aeruginosa keratitis. Mol Vis 19: 1502-1514.
Dugo L, Collin M, Allen DA, Patel NS, Bauer I, Mervaala EM, Louhelainen M, Foster SJ, Yaqoob MM, Thiemermann C (2005) GSK-3beta inhibitors attenuate the organ injury/ /dysfunction caused by endotoxemia in the rat. Crit Care Med 33: 1903-1912.
Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (2000) Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 406: 86-90.
Hoffmeister L, Diekmann M, Brand K, Huber R (2020) GSK3: a kinase balancing promotion and resolution Jope RS, Cheng Y, Lowell JA, Worthen RJ, Sitbon YH, Beurel E (2017) Stressed and inflamed, can GSK3 be blamed? Trends Biochem Sci 42: 180-192.
Jope RS, Yuskaitis CJ, Beurel E (2007) Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res 32: 577-595.
Hu P, Huang F, Niu J, Tang Z (2015) TLR-4 involvement in pyroptosis of mice with pulmonary inflammation infected by Actinobacillus pleuropneumoniae. Wei Sheng Wu Xue Bao 55: 650-656.
Kumar V (2018) Toll-like receptors in immunity and inflammatory diseases: past, present, and future. Int Immunopharmacol 59: 391-412.
Kumar V (2020) Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets. Int Immunopharmacol 89: 107087.
Li B, Fang J, Zuo Z, Yin S, He T, Yang M, Deng J, Shen L, Ma X, Yu S, Wang Y, Ren Z (2018) Activation of porcine alveolar macrophages by Actinobacillus pleuropneumoniae lipopolysaccharide via the toll-like receptor 4/NF-kappaB-mediated pathway. Infect Immun 86: e00642-17.
Li H, Gao D, Li Y, Wang Y, Liu H, Zhao J (2018) Antiviral effect of lithium chloride on porcine epidemic diarrhea virus in Vitro. Res Vet Sci 118: 288-294.
Li N, Zhang X, Dong H, Zhang S, Sun J, Qian Y (2016) Lithium ameliorates LPS-induced astrocytes activation partly via inhibition of toll-Like receptor 4 expression. Cell Physiol Biochem 38: 714-725.
Liu X, Klein PS (2018) Glycogen synthase kinase-3 and alternative splicing. Wiley Interdiscip Rev RNA 9: e1501.
Makola RT, Mbazima VG, Mokgotho MP, Gallicchio VS, Matsebatlela TM (2020) The effect of lithium on inflammation-associated genes in lipopolysaccharide-activated Raw 264.7 macrophages. Int J Inflam 2020: 8340195.
Martin M, Rehani K, Jope RS, Michalek SM (2005) Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol. 6: 777-784.
Medunjanin S, Schleithoff L, Fiegehenn C, Weinert S, Zuschratter W, Braun-Dullaeus RC (2016) GSK-3β controls NF-kappaB activity via IKKγ/NEMO. Sci Rep 6: 38553.
Oviedo-Boyso J, Cortés-Vieyra R, Huante-Mendoza A, Yu HB, Valdez-Alarcón JJ, Bravo-Patiño A, Cajero- -Juárez M, Finlay BB, Baizabal-Aguirre VM (2011) The phosphoinositide-3-kinase-Akt signalling pathway is important for Staphylococcus aureus internalization by endothelial cells. Infect Immun 79: 4569-4577.
Paramel GV, Sirsjö A, Fransén K (2015) Role of genetic alterations in the NLRP3 and CARD8 genes in health and disease. Mediators Inflamm 2015: 846782.
Pereira MF, Rossi CC, Seide LE, Martins Filho S, Dolinski CM, Bazzolli DM (2018) Antimicrobial resistance, biofilm formation and virulence reveal Actinobacillus pleuropneumoniae strains’ pathogenicity complexity. Res Vet Sci 118: 498-501.
Raghavendra PB, Lee E, Parameswaran N (2014) Regulation of macrophage biology by lithium: a new look at an old drug. J Neuroimmune Pharmacol 9: 277-284.
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49: 1603-1616.
Sassu EL, Bossé JT, Tobias TJ, Gottschalk M, Langford PR, Hennig-Pauka I (2018) Update on Actinobacillus pleuropneumoniae- knowledge, gaps and challenges. Transbound Emerg Dis 65 (Suppl 1): 72-90.
Snitow ME, Bhansali RS, Klein PS (2021) Lithium and therapeutic targeting of GSK-3. Cells 10: 255.
Song J, Bishop BL, Li G, Duncan MJ, Abraham SN (2007) TLR4 initiated and cAMP-mediated abrogation of bacterial invasion of the bladder. Cell Host Microbe 1: 287-298. Woodgett JR, Ohashi PS (2005) GSK3: an in-Toll-erant protein kinase? Nat Immunol 6: 751-752.
Zhang P, Katz J, Michalek SM (2009) Glycogen synthase kinase-3beta (GSK3beta) inhibition suppresses the inflammatory response to Francisella infection and protects against tularemia in mice. Mol Immunol 46: 677-687.
Zhao Y, Yan K, Wang Y, Cai J, Wei L, Li S, Xu W, Li M (2020) Lithium chloride confers protection against viral myocarditis via suppression of coxsackievirus B3 virus replication. Microb Pathog 144: 104169. of inflammation. Cells 9: 820.






DOI: 10.24425/pjvs.2022.140838