The protease inhibitor cystatin C down‐regulates the release of IL‐β and TNF‐α in lipopolysaccharide activated monocytes

  title={The protease inhibitor cystatin C down‐regulates the release of IL‐$\beta$ and TNF‐$\alpha$ in lipopolysaccharide activated monocytes},
  author={Susanne Thiesen Gren and Sabina Janciauskiene and Salipalli Sandeep and Danny D. Jonigk and Peter Helding Kvist and Jens Gammeltoft Gerwien and Katarina H{\aa}kansson and Olof Grip},
  journal={Journal of Leukocyte Biology},
Human cystatin C, a member of the cysteine proteinase‐inhibitory family, is produced by all nucleated cells and has important roles in regulating natural immunity. Nematode homologs to human cystatin C have been shown to have anti‐inflammatory effects on monocytes and to reduce colitis in mice. In Crohn's disease, pathogenic activated monocytes help drive inflammatory processes via the release of proinflammatory cytokines and chemokines. In particular, tumor necrosis factor‐α–producing… 

Cystatin C Deficiency Increases LPS-Induced Sepsis and NLRP3 Inflammasome Activation in Mice

It is demonstrated that the excessive inflammatory response to the LPS-induced sepsis in CstC KO mice is dependent on increased caspase-11 expression and impaired autophagy, but is not associated with increased cysteine cathepsin activity.

Inhibition of lipopolysaccharide‐induced osteoclast formation and bone resorption in vitro and in vivo by cysteine proteinase inhibitors

It is concluded that cysteine proteinase inhibitors effectively inhibit LPS‐induced osteoclast formation in vivo and in vitro by inhibition of TNF‐α expression.

Secreted cystatins decrease proliferation and enhance apoptosis of human leukemic cells

External addition of cystatins C and D to HL‐60 and Jurkat cells demonstrated similar degrees of cystatin D uptake and decreased viability as for U937 cells, indicating that these effects are general for leukemic cells.

The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function

The aim of the present article is to review the mechanisms of dysregulation of cysteine cathepsins and their inhibitors in relation to immune dysfunction to address new possibilities for regulation of their function.

Antimicrobial and anti-inflammatory activity of Cystatin C on human gingival fibroblast incubated with Porphyromonas gingivalis

Information on the antimicrobial and immunomodulatory properties of cystatin C could aid in the design of new therapeutic approaches to facilitate the elimination of this bacterium to improve the treatment of periodontal disease.

Obesity-Induced Increase in Cystatin C Alleviates Tissue Inflammation

CysC is upregulated under obesity conditions and thereby counteracts inflammation of peripheral insulin-sensitive tissues and, thus, obesity-associated deterioration of glucose metabolism.

Correlation between intestinal flora and serum inflammatory factors in patients with Crohn's disease.

It is concluded that monitoring the changes in distribution and composition of intestinal flora as well as the levels of blood inflammatory factors could play a significant role in the treatment process of Crohn's disease.



Macrophage responses to interferon-gamma are dependent on cystatin C levels.

Regulation of TNF‐α with a focus on rheumatoid arthritis

The role and regulation of the major proinflammatory cytokine TNF‐α, in particular the regulation of T NF‐α production, post‐translational processing and signaling of TNF-α and its receptors are discussed.

A filarial cysteine protease inhibitor down‐regulates T cell proliferation and enhances interleukin‐10 production

A 17‐kDa antigen (Av17) of the rodent filarial parasite Acanthocheilonema viteae is described, which shows amino acid homologies to cystatin C, a major cysteine protease inhibitor belonging to family 2 of the Cystatin superfamily, a likely effector molecule of immunomodulation and a potential target for antifilarial intervention.

Cystatin C antagonizes transforming growth factor beta signaling in normal and cancer cells.

It is shown that CystC antagonized TGF-beta binding to its cell surface receptors, doing so by interacting physically with the T GF-beta type II receptor and antagonizing its binding of TGF -beta.

Modulation of dendritic cell function and immune response by cysteine protease inhibitor from murine nematode parasite Heligmosomoides polygyrus

It is demonstrated that the CPI from nematode parasites is able to modulate differentiation and activation stages of BMDC and interferes with antigen and MHC‐II molecule processing and Toll‐like receptor signalling pathway, resulting in functionally deficient DC that induce a suboptimum immune response.

Tumor necrosis factor alpha and adalimumab differentially regulate CD36 expression in human monocytes

In chronic inflammatory diseases, such as rheumatoid arthritis, inflammation acts as an independent cardiovascular risk factor and the use of anti-inflammatory drugs, such as anti-tumor necrosis

Cystatins of filarial nematodes up‐regulate the nitric oxide production of interferon‐γ‐activated murine macrophages

The data suggest that filarial cystatins are potent triggers of the production of NO, a mediator which was shown to have a role as an effector molecule against filarial worms in vitro and in vivo.

Up‐regulation of human monocyte CD163 upon activation of cell‐surface Toll‐like receptors

It is reported that the TLR2 and TLR5 agonists—Pam3Cys and bacterial flagellin—have similar effects on CD163 surface expression, demonstrating that surface CD163 expression on mononuclear phagocytes is a carefully regulated component of the innate immune response to infection.

Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling

  • F. StrålbergP. Henning U. Lerner
  • Biology, Medicine
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2013
The cysteine proteinase inhibitor cystatin C inhibited RANKL‐stimulated osteoclast formation in mouse bone marrow macrophage cultures, an effect associated with decreased mRNA expression of Acp5,

TNF‐mediated inflammatory disease

  • J. Bradley
  • Biology, Medicine
    The Journal of pathology
  • 2008
The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of T NF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis.