Dihydroartemisinin ameliorates innate inflammatory response induced by <i>Streptococcus</i> <i>suis</i>-derived muramidase-released protein via inactivation of TLR4-dependent NF-κB signaling

Yun Ji; Kaiji Sun; Ying Yang; Zhenlong Wu

doi:10.1016/j.jpha.2023.05.013

Volume 13 Issue 10

Oct. 2023

Turn off MathJax

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(10): 1183-1194

Yun Ji, Kaiji Sun, Ying Yang, Zhenlong Wu. Dihydroartemisinin ameliorates innate inflammatory response induced by Streptococcus suis-derived muramidase-released protein via inactivation of TLR4-dependent NF-κB signaling[J]. Journal of Pharmaceutical Analysis, 2023, 13(10): 1183-1194. doi: 10.1016/j.jpha.2023.05.013

Citation:

Yun Ji, Kaiji Sun, Ying Yang, Zhenlong Wu. Dihydroartemisinin ameliorates innate inflammatory response induced by Streptococcus suis-derived muramidase-released protein via inactivation of TLR4-dependent NF-κB signaling[J]. Journal of Pharmaceutical Analysis, 2023, 13(10): 1183-1194. doi: 10.1016/j.jpha.2023.05.013

Citation:

PDF( 5926 KB)

Dihydroartemisinin ameliorates innate inflammatory response induced by Streptococcus suis-derived muramidase-released protein via inactivation of TLR4-dependent NF-κB signaling

doi: 10.1016/j.jpha.2023.05.013

Yun Ji^a,
Kaiji Sun^a,
Ying Yang^{a
,
,},
Zhenlong Wu^a,b

a. State Key Laboratory of Animal Nutrition and Feeding, China Agricultural University, Beijing, 100193, China;
b. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, China

Funds:

This work was supported by the National Key R&D Program of China (Grant Nos.: 2022YFF1100104 and 2022YFF1100102), the National Natural Science Foundation of China (Grant Nos.: 31625025, 32172749, and 32202701), the 2115 Talent Development Program of China Agricultural University (Grant No.: 00109016), and the Zhengzhou 1125 Talent Program, China (Grant No.: 2016XT016).

Received Date: Dec. 17, 2022
Accepted Date: May 26, 2023
Rev Recd Date: May 17, 2023
Publish Date: Oct. 30, 2023

Abstract

Abstract

Muramidase-released protein (MRP) is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis (S. suis). However, the identification of viable therapeutics for S. suis infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation. Dihydroartemisinin (DhA) is an artemisinin derivative with potential anti-inflammatory activity. The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure. This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages. With the candidate mechanism in mind, we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP. The innate immune response in mice was drastically triggered by MRP, manifesting as splenic and systemic inflammation with splenomegaly, immune cell infiltration, and an elevation in pro-inflammatory cytokines. A crucial role for Toll-like receptor 4 (TLR4) in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B (NF-κB) activation was revealed by TLR4 blockade. In addition, NF-κB-dependent transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinases (MAPKs) activation was required for the inflammatory signal transduction engendered by MRP. Intriguingly, we observed an alleviation effect of DhA on the MRP-induced immune response, which referred to the suppression of TLR4-mediated actuation of NF-κB-STAT3/MAPK cascades. The inflammatory response elicited by MRP is relevant to TLR4-dependent NF-κB activation, followed by an increase in the activity of STAT3 or MAPKs. DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade, highlighting the therapeutic potential of DhA in targeting S. suis infection diseases.
- Dihydroartemisinin,
- Inflammation,
- Muramidase-released protein,
- Streptococcus suis,
- Toll-like receptor 4

FullText(HTML)

References(45)

References

J. Dutkiewicz, J. Sroka, V. Zajac, et al., Streptococcus suis: a re-emerging pathogen associated with occupational exposure to pigs or pork products. Part I - Epidemiology, Ann. Agric. Environ. Med. 24 (2017) 683-695.

G. Goyette-Desjardins, J.P. Auger, J. Xu, et al., Streptococcus suis, an important pig pathogen and emerging zoonotic agent-an update on the worldwide distribution based on serotyping and sequence typing, Emerg. Microbes Infect. 3 (2014), e45.

N. Fittipaldi, M. Segura, D. Grenier, et al., Virulence factors involved in the pathogenesis of the infection caused by the swine pathogen and zoonotic agent Streptococcus suis, Future Microbiol. 7 (2012) 259-279.

M. Gottschalk, J. Xu, C. Calzas, et al., Streptococcus suis: a new emerging or an old neglected zoonotic pathogen? Future Microbiol. 5 (2010) 371-391.

A.G. Tsiotou, G.H. Sakorafas, G. Anagnostopoulos, et al., Septic shock; current pathogenetic concepts from a clinical perspective, Med. Sci. Monit. 11 (2005) RA76-RA85.

M. Segura, G. Vanier, D. Al-Numani, et al., Proinflammatory cytokine and chemokine modulation by Streptococcus suis in a whole-blood culture system, FEMS Immunol. Med. Microbiol. 47 (2006) 92-106.

T. Tenenbaum, T.M. Asmat, M. Seitz, et al., Biological activities of suilysin: role in Streptococcus suis pathogenesis, Future Microbiol. 11 (2016) 941-954.

E. Vinogradov, G. Goyette-Desjardins, M. Okura, et al., Structure determination of Streptococcus suis serotype 9 capsular polysaccharide and assignment of functions of the cps locus genes involved in its biosynthesis, Carbohydr. Res. 433 (2016) 25-30.

C.G. Baums, G.J. Verkuhlen, T. Rehm, et al., Prevalence of Streptococcus suis genotypes in wild boars of northwestern Germany, Appl. Environ. Microbiol. 73 (2007) 711-717.

Q. Li, Y. Fu, C. Ma, et al., The non-conserved region of MRP is involved in the virulence of Streptococcus suis serotype 2, Virulence 8 (2017) 1274-1289.

C. Schwerk, Muramidase-released protein of Streptococcus suis: new insight into its impact on virulence, Virulence 8 (2017) 1078-1080.

J. Wang, D. Kong, S. Zhang, et al., Interaction of fibrinogen and muramidase-released protein promotes the development of Streptococcus suis meningitis, Front. Microbiol. 6 (2015), 1001.

Y. Pian, P. Wang, P. Liu, et al., Proteomics identification of novel fibrinogen-binding proteins of Streptococcus suis contributing to antiphagocytosis, Front. Cell. Infect. Microbiol. 5 (2015), 19.

L. Ferrero-Miliani, O.H. Nielsen, P.S. Andersen, et al., Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation, Clin. Exp. Immunol. 147 (2007) 227-235.

M.P. Lecours, M. Segura, N. Fittipaldi, et al., Immune receptors involved in Streptococcus suis recognition by dendritic cells, PLoS One 7 (2012), e44746.

A. Wojtkowiak-Giera, M. Derda, D. Kosik-Bogacka, et al., Influence of Artemisia annua L. on toll-like receptor expression in brain of mice infected with Acanthamoeba sp, Exp. Parasitol. 185 (2018) 17-22.

C. Wu, J. Liu, X. Pan, et al., Design, synthesis and evaluation of the antibacterial enhancement activities of amino dihydroartemisinin derivatives, Molecules 18 (2013) 6866-6882.

X. Huang, Z. Xie, F. Liu, et al., Dihydroartemisinin inhibits activation of the Toll-like receptor 4 signaling pathway and production of type I interferon in spleen cells from lupus-prone MRL/lpr mice, Int. Immunopharmacol. 22 (2014) 266-272.

B. Li, R. Zhang, J. Li, et al., Antimalarial artesunate protects sepsis model mice against heat-killed Escherichia coli challenge by decreasing TLR4, TLR9 mRNA expressions and transcription factor NF-kappa B activation, Int. Immunopharmacol. 8 (2008) 379-389.

H.G. Kim, J.H. Yang, E.H. Han, et al., Inhibitory effect of dihydroartemisinin against phorbol ester-induced cyclooxygenase-2 expression in macrophages, Food Chem. Toxicol. 56 (2013) 93-99.

M. Wei, X. Xie, X. Chu, et al., Dihydroartemisinin suppresses ovalbumin-induced airway inflammation in a mouse allergic asthma model, Immunopharmacol. Immunotoxicol. 35 (2013) 382-389.

L. Jia, Q. Song, C. Zhou, et al., Dihydroartemisinin as a putative STAT3 inhibitor, suppresses the growth of head and neck squamous cell carcinoma by targeting Jak2/STAT3 signaling, PLoS One 11 (2016), e0147157.

K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT Method, Methods 25 (2001) 402-408.

Q. Li, H. Liu, D. Du, et al., Identification of novel laminin- and fibronectin-binding proteins by far-Western blot: Capturing the adhesins of Streptococcus suis type 2, Front. Cell. Infect. Microbiol. 5 (2015), 82.

E.A. Ivanova, A.N. Orekhov, Monocyte activation in immunopathology: Cellular test for development of diagnostics and therapy, J. Immunol. Res. 2016 (2016), 4789279.

A. Lavagna, J.P. Auger, A. Dumesnil, et al., Interleukin-1 signaling induced by Streptococcus suis serotype 2 is strain-dependent and contributes to bacterial clearance and inflammation during systemic disease in a mouse model of infection, Vet. Res. 50 (2019), 52.

L. Zhang, J. Wang, W. Xu, et al., Magnolol inhibits Streptococcus suis-induced inflammation and ROS formation via TLR2/MAPK/NF-κB signaling in RAW264.7 cells, Pol. J. Vet. Sci. 21 (2018) 111-118.

Y. Zheng, Y. Li, X. Ran, et al., Mettl14 mediates the inflammatory response of macrophages in atherosclerosis through the NF-κB/IL-6 signaling pathway, Cell. Mol. Life Sci. 79 (2022), 311.

R. Graveline, M. Segura, D. Radzioch, et al., TLR2-dependent recognition of Streptococcus suis is modulated by the presence of capsular polysaccharide which modifies macrophage responsiveness, Int. Immunol. 19 (2007) 375-389.

R. Li, A. Zhang, B. Chen, et al., Response of swine spleen to Streptococcus suis infection revealed by transcription analysis, BMC Genomics 11 (2010), 556.

Q. Zhang, Y. Yang, S. Yan, et al., A novel pro-inflammatory protein of Streptococcus suis 2 induces the Toll-like receptor 2-dependent expression of pro-inflammatory cytokines in RAW 264.7 macrophages via activation of ERK1/2 pathway, Front. Microbiol. 6 (2015), 178.

Q. Zhang, J. Huang, J. Yu, et al., HP1330 contributes to Streptococcus suis virulence by inducing Toll-like receptor 2- and ERK1/2-dependent pro-inflammatory responses and influencing in vivo S. suis loads, Front. Immunol. 8 (2017), 869.

Z. Wang, M. Guo, L. Kong, et al., TLR4 agonist combined with trivalent protein JointS of Streptococcus suis provides immunological protection in animals, Vaccines (Basel) 9 (2021), 184.

L. Bi, Y. Pian, S. Chen, et al., Toll-like receptor 4 confers inflammatory response to Suilysin, Front. Microbiol. 6 (2015), 644.

S.M. Opal, C.E. Huber, Bench-to-bedside review: toll-like receptors and their role in septic shock, Crit. Care 6 (2002) 125-136.

S. Samarpita, J.Y. Kim, M.K. Rasool, et al., Investigation of toll-like receptor (TLR) 4 inhibitor TAK-242 as a new potential anti-rheumatoid arthritis drug, Arthritis Res. Ther. 22 (2020), 16.

F. Ma, X. Chang, G. Wang, et al., Streptococcus suis serotype 2 stimulates neutrophil extracellular traps formation via activation of p38 MAPK and ERK1/2, Front. Immunol. 9 (2018), 2854.

H. Zheng, H. Sun, M.C. Dominguez-Punaro, et al., Evaluation of the pathogenesis of meningitis caused by Streptococcus suis sequence type 7 using the infection of BV2 microglial cells, J. Med. Microbiol. 62 (2013) 360-368.

L. Swanson, G.D. Katkar, J. Tam, et al., TLR4 signaling and macrophage inflammatory responses are dampened by GIV/Girdin, Proc. Natl. Acad. Sci. U S A 117 (2020) 26895-26906.

M. Soutto, N. Bhat, S. Khalafi, et al., NF-kB-dependent activation of STAT3 by H. pylori is suppressed by TFF1, Cancer Cell Int. 21 (2021), 444.

L. Liu, H. Guo, A. Song, et al., Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways, BMC Immunol. 21 (2020), 32.

Y.G. Zhao, Y. Wang, Z. Guo, et al., Dihydroartemisinin ameliorates inflammatory disease by its reciprocal effects on Th and regulatory T cell function via modulating the mammalian target of rapamycin pathway, J. Immunol. 189 (2012) 4417-4425.

S.C. Yan, Y.J. Wang, Y.J. Li, et al., Dihydroartemisinin regulates the Th/Treg balance by inducing activated CD4+ T cell apoptosis via heme oxygenase-1 induction in mouse models of inflammatory bowel disease, Molecules 24 (2019), 2475.

Y. Niu, Y. Zhao, J. He, et al., Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4/NOD/NF-κB signaling pathway in weaned piglets with intrauterine growth retardation, Anim. Nutr. 7 (2021) 667-678.

T. Zhang, X. Zhang, C. Lin, et al., Artemisinin inhibits TLR4 signaling by targeting co-receptor MD2 in microglial BV-2 cells and prevents lipopolysaccharide-induced blood-brain barrier leakage in mice, J. Neurochem. 157 (2021) 611-623.

Relative Articles

Supplements(0)

Cited By

Proportional views