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Rho-kinase regulate...
Rho-kinase regulates induction of T-cell immune dysfunction in abdominal sepsis.
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- Hasan, Zirak (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Palani, Karzan (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Zhang, Songen (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Lepsenyi, Mattias (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Hwaiz, Rundk (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Rahman, Milladur (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Syk, Ingvar (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Jeppsson, Bengt (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Thorlacius, Henrik (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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(creator_code:org_t)
- 2013
- 2013
- Engelska.
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Ingår i: Infection and Immunity. - 1098-5522. ; 81:7, s. 2499-2506
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- T-cell dysfunction increases susceptibility to infections in patients with sepsis. In the present study, we hypothesized that Rho-kinase signaling might regulate induction of T-cell dysfunction in abdominal sepsis. Male C57BL/6 mice were treated with the specific Rho-kinase inhibitor Y-27632 (5 mg/kg) prior to cecal ligation and puncture (CLP). Spleen CD4 T-cell apoptosis, proliferation and regulatory T-cells (CD4(+)CD25(+)Foxp3(+)) were determined by flow cytometry. Formation of IFN-γ and IL-4 in the spleen and plasma levels of HMBG1 and IL-6 were quantified by use of ELISA. It was found that CLP evoked apoptosis and decreased proliferation in splenic CD4 T-cells. Inhibition of Rho-kinase activity decreased apoptosis and enhanced proliferation of CD4 T-cells in septic animals. In addition, CLP-evoked induction of regulatory T-cells in the spleen was abolished by Rho-kinase inhibition. CLP reduced the levels of IFN-γ and IL-4 in the spleen. Pretreatment with Y-27632 inhibited the sepsis-induced decrease in IFN-γ but not IL-4 formation in the spleen. CLP increased plasma levels of HMGB1 by 20-fold and IL-6 by 19-fold. Inhibition of Rho-kinase decreased this CLP-evoked increase of HMGB1, IL-6 and IL-17 levels in the plasma by more than 60%, suggesting that Rho-kinase regulates systemic inflammation in sepsis. Moreover, we observed that pretreatment with Y-27632 abolished CLP-induced bacteremia. Together, our novel findings indicate that Rho-kinase is a powerful regulator of T-cell immune dysfunction in abdominal sepsis. Thus, targeting Rho-kinase signaling might be a useful strategy to improve T-cell immunity in patients with abdominal sepsis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
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