Open AccessCaspase‐8 regulates the expression of pro‐ and anti‐inflammatory cytokines in human bone marrow‐derived mesenchymal stromal cells
Author(s) -
Moen Siv H.,
Westhrin Marita,
Zahoor Muhammad,
Nørgaard Nikolai N.,
Hella Hanne,
Størdal Berit,
Sundan Anders,
Nilsen Nadra J.,
Sponaas AnneMarit,
Standal Therese
Publication year - 2016
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.117
Subject(s) - mesenchymal stem cell , stromal cell , bone marrow , human bone , proinflammatory cytokine , cancer research , microbiology and biotechnology , inflammation , immunology , biology , in vitro , biochemistry
Mesenchymal stem cells, also called mesenchymal stromal cells, MSCs, have great potential in stem cell therapy partly due to their immunosuppressive properties. How these cells respond to chronic inflammatory stimuli is therefore of importance. Toll‐like receptors (TLR)s are innate immune receptors that mediate inflammatory signals in response to infection, stress, and damage. Caspase‐8 is involved in activation of NF‐kB downstream of TLRs in immune cells. Here we investigated the role of caspase‐8 in regulating TLR‐induced cytokine production from human bone marrow‐derived mesenchymal stromal cells (hBMSCs). Methods Cytokine expression in hBMCs in response to poly(I:C) and LPS was evaluated by PCR, multiplex cytokine assay, and ELISA. TLR3, TRIF, and caspase‐8 were silenced using siRNA. Caspase‐8 was also inhibited using a caspase‐8 inhibitor, z‐IEDT. Results We found that TLR3 agonist poly(I:C) and TLR4 agonist LPS induced secretion of several pro‐inflammatory cytokines in a TLR‐dependent manner which required the TLR signaling adaptor molecule TRIF. Further, poly(I:C) reduced the expression of anti‐inflammatory cytokines HGF and TGFβ whereas LPS reduced HGF expression only. Notably, caspase‐8 was involved in the induction of IL‐ IL‐1β, IL‐6, CXCL10, and in the inhibition of HGF and TGFβ. Conclusion Caspase‐8 appears to modulate hBMSCs into gaining a pro‐inflammatory phenotype. Therefore, inhibiting caspase‐8 in hBMSCs might promote an immunosuppressive phenotype which could be useful in clinical applications to treat inflammatory disorders.