Abstract
Extracellular Hsp70 (eHsp70) is elevated in blood of patients with inflammatory diseases (e.g. chronic obstructive pulmonary disease), prone to bacterial infections. It stimulates pro-inflammatory effects in cells via TLR2 and TLR4. The main hypothesis was that eHsp70 induces inflammation and alters inflammatory responses to lipopolysaccharide (LPS) and lipoteichoic acid (LTA). We assessed pro-inflammatory cytokines concentrations, TLR2, TLR4 and Hsp70 mRNA expressions, NF-κB and MAPKs activation, and viability after treatment of monocyte-derived macrophages (MDMs) and THP-1 cells with recombinant human (rh) Hsp70, LPS and LTA. rhHsp70, LPS, LTA and their combinations induced IL-6, IL-8 and TNF-α from MDMs. LPS, LTA, and combinations with rhHsp70 increased TLR2 and decreased TLR4 in both cells. rhHsp70 increased TLR2 and TLR4 in THP-1 cells, and TLR2 in MDMs. rhHsp70, LPS and their combinations up-regulated Hsp70 in MDMs, while down-regulated it in THP-1. LPS and its combinations with rhHsp70 lowered cell viability in THP-1 cells and activated caspases-8 and -9. Involvement of NF-κB and MAPKs in inflammatory and survival mechanisms stimulated by rhHsp70 was demonstrated. eHsp70 alone and in combination with bacterial components could provoke inflammation and affect viability of MDMs and THP-1 cells leading to disturbed inflammatory responses in diseases accompanied with bacterial colonisations or infections.
Funding source: Hrvatska Zaklada za Znanost
Award Identifier / Grant number: IP-2014-09-1247
Funding source: Young researchers’ career development project – training of doctoral students
Acknowledgments
This work has been fully supported by the Croatian Science Foundation under the project number IP-2014-09-1247. The work of PhD student Iva Hlapčić has been fully supported by the “Young researchers’ career development project – training of doctoral students ” of the Croatian Science Foundation funded by the European Union from the European Social Fund.
Competing interests: The authors declare that they have no conflict of interest.
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