Alarmins firing arthritis: Helpful diagnostic tools and promising therapeutic targets

Lavrič, Miha; Miranda-García, María Auxiliadora; Holzinger, Dirk; Foell, Dirk; Wittkowski, Helmut

doi:10.1016/j.jbspin.2016.06.010

Cited by 17 publications

(17 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…by competing with the receptor for ligand binding. Furthermore, the finding that high levels of the DAMP molecule, HMGB1 ( 62 ), which was recently identified as a potential natural ligand of TREM-1 in mice ( 46 ), are present in the SF of OJIA patients [this study and Ref ( 86 ). ], confirms the release of TREM-1 putative ligands in the inflamed arthritic environment, warranting future in-depth studies of TREM-1 activation in synovial Mf.…”

Section: Discussionmentioning

confidence: 88%

“…Previous reports have suggested a role for TREM-1 in the recognition of DAMPs ( 45 , 56 ), endogenous molecules released by activated inflammatory and/or damaged/necrotic cells and implicated to the initiation and perpetuation of the inflammatory process in various inflammatory arthritic diseases ( 62 ). In particular, the nuclear DNA-binding protein, HMGB1, has been recently identified as a natural ligand of TREM-1 in mice ( 46 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

et al. 2017

View full text Add to dashboard Cite

Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM)-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

et al. 2017

View full text Add to dashboard Cite

show abstract

“…On the other hand, IL-33 acts as an alarmin: necrotic cells release the integral bioactive form of IL-33, which functions as an endogenous warning signal. The increased expression of IL-33 after cell death causes the induction of other cytokines, including IL-31 [133][134][135]. In particular, IL-33 promotes IL-4 dependent release of IL-31 by CD4+ Th cells.…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

IL-33/IL-31 Axis in Osteoporosis

Martinis

Sirufo

Suppa

et al. 2020

IJMS

View full text Add to dashboard Cite

The study of the immunoskeletal interface has led to the discovery of numerous cytokines involved in the regulation of bone remodeling, providing valuable information on the pathogenesis of osteoporosis. The role of inflammatory cytokines of the Th1 and Th17 profile in osteoporosis is well known. Here we focus on two newly discovered Th2 cytokines, IL-31 and IL-33, whose implications in osteoporosis are recently emerging. Clinical and experimental observations suggest an important role of the IL-33/IL-31 axis in osteoporosis. IL-33 induces IL-31 secretion by Th2 cells and inhibits RANKL-dependent osteoclastogenesis, thus counteracting bone loss. IL-31 influences Th1/Th17 osteoclastogenetic inflammation and limits Th2 osteoprotective processes, thus favoring osteoporosis. Better knowledge of the role of IL-31 and IL-33 and their receptor complexes in osteoporosis could provide an interesting perspective for the development of new and more effective therapies, possibly with less side effects.

show abstract

“…Calprotectin is a member of the S100 protein family and is a heterodimeric complex of S100A8 and S100A9 proteins (calgranulin A and B, part of the Alarmins) [6]. Calprotectin is a calcium and zinc binding protein in the cytosol of monocytes, macrophages and neutrophil granulocytes.…”

mentioning

confidence: 99%