Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group a streptococcal infection

Shiou Ling Lu, Chiau Yuang Tsai, Yueh Hsia Luo, Chih Feng Kuo, Wei Chieh Lin, Yu Tzu Chang, Jiunn Jong Wu, Woei Jer Chuang, Ching Chuan Liu, Lee Chao, Julie Chao, Yee Shin Lin

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Group A streptococcus (GAS) infection may cause severe life-threatening diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Despite the availability of effective antimicrobial agents, there has been a worldwide increase in the incidence of invasive GAS infection. Kallistatin (KS), originally found to be a tissue kallikrein-binding protein, has recently been shown to possess anti-inflammatory properties. However, its efficacy in microbial infection has not been explored. In this study, we transiently expressed the human KS gene by hydrodynamic injection and investigated its anti-inflammatory and protective effects in mice via air pouch inoculation of GAS. The results showed that KS significantly increased the survival rate of GAS-infected mice. KS treatment reduced local skin damage and bacterial counts compared with those in mice infected with GAS and treated with a control plasmid or saline. While there was a decrease in immune cell infiltration of the local infection site, cell viability and antimicrobial factors such as reactive oxygen species actually increased after KS treatment. The efficiency of intracellular bacterial killing in neutrophils was directly enhanced by KS administration. Several inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1, and interleukin 6, in local infection sites were reduced by KS. In addition, KS treatment reduced vessel leakage, bacteremia, and liver damage after local infection. Therefore, our study demonstrates that KS provides protection in GAS-infected mice by enhancing bacterial clearance, as well as reducing inflammatory responses and organ damage.

Original languageEnglish
Pages (from-to)5366-5372
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume57
Issue number11
DOIs
Publication statusPublished - 2013 Nov 1

Fingerprint

Streptococcal Infections
Anti-Inflammatory Agents
Streptococcus
Infection
kallistatin
Necrotizing Fasciitis
Bacterial Load
Hydrodynamics
Septic Shock
Bacteremia
Anti-Infective Agents
Interleukin-1
Interleukin-6
Reactive Oxygen Species
Cell Survival
Neutrophils
Plasmids
Therapeutics
Tumor Necrosis Factor-alpha
Air

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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title = "Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group a streptococcal infection",
abstract = "Group A streptococcus (GAS) infection may cause severe life-threatening diseases, including necrotizing fasciitis and streptococcal toxic shock syndrome. Despite the availability of effective antimicrobial agents, there has been a worldwide increase in the incidence of invasive GAS infection. Kallistatin (KS), originally found to be a tissue kallikrein-binding protein, has recently been shown to possess anti-inflammatory properties. However, its efficacy in microbial infection has not been explored. In this study, we transiently expressed the human KS gene by hydrodynamic injection and investigated its anti-inflammatory and protective effects in mice via air pouch inoculation of GAS. The results showed that KS significantly increased the survival rate of GAS-infected mice. KS treatment reduced local skin damage and bacterial counts compared with those in mice infected with GAS and treated with a control plasmid or saline. While there was a decrease in immune cell infiltration of the local infection site, cell viability and antimicrobial factors such as reactive oxygen species actually increased after KS treatment. The efficiency of intracellular bacterial killing in neutrophils was directly enhanced by KS administration. Several inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1, and interleukin 6, in local infection sites were reduced by KS. In addition, KS treatment reduced vessel leakage, bacteremia, and liver damage after local infection. Therefore, our study demonstrates that KS provides protection in GAS-infected mice by enhancing bacterial clearance, as well as reducing inflammatory responses and organ damage.",
author = "Lu, {Shiou Ling} and Tsai, {Chiau Yuang} and Luo, {Yueh Hsia} and Kuo, {Chih Feng} and Lin, {Wei Chieh} and Chang, {Yu Tzu} and Wu, {Jiunn Jong} and Chuang, {Woei Jer} and Liu, {Ching Chuan} and Lee Chao and Julie Chao and Lin, {Yee Shin}",
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Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group a streptococcal infection. / Lu, Shiou Ling; Tsai, Chiau Yuang; Luo, Yueh Hsia; Kuo, Chih Feng; Lin, Wei Chieh; Chang, Yu Tzu; Wu, Jiunn Jong; Chuang, Woei Jer; Liu, Ching Chuan; Chao, Lee; Chao, Julie; Lin, Yee Shin.

In: Antimicrobial agents and chemotherapy, Vol. 57, No. 11, 01.11.2013, p. 5366-5372.

Research output: Contribution to journalArticle

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T1 - Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group a streptococcal infection

AU - Lu, Shiou Ling

AU - Tsai, Chiau Yuang

AU - Luo, Yueh Hsia

AU - Kuo, Chih Feng

AU - Lin, Wei Chieh

AU - Chang, Yu Tzu

AU - Wu, Jiunn Jong

AU - Chuang, Woei Jer

AU - Liu, Ching Chuan

AU - Chao, Lee

AU - Chao, Julie

AU - Lin, Yee Shin

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