Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

Steiner, Stefanie; Daniel, Carolin; Fischer, Anika; Atreya, Imke; Hirschmann, Simon; Waldner, Maximilian J.; Neumann, Helmut; Atreya, Raja; Weigmann, Benno

doi:10.1007/s00005-014-0309-7

Cited by 14 publications

(6 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present data reveal that the serum levels of proinflammatory cytokine IL-13 is higher in IBD patients than healthy subjects. Such a phenomenon was also found by other investigators [Steiner et al, 2015]. The significance of this finding is that IL-13 can inhibit the expression of cyp27b1 in CD14 þ cells.…”

Section: Discussionsupporting

confidence: 86%

Interleukin-13 Inhibits Expression of cyp27b1 in Peripheral CD14+ Cells That Is Correlated With Vertebral Bone Mineral Density of Patients With Ulcerative Colitis

Ding

Zhou

et al. 2016

J. Cell. Biochem.

View full text Add to dashboard Cite

Osteoporosis is a common problem in aged people and those with related diseases, such as inflammatory bowel diseases. Deregulation of vitamin D metabolism plays a role in the pathogenesis of osteoporosis. Micro RNA (miR) can regulate cytokine expression in cells. This study test a hypothesis that inflammatory cytokine interleukin (IL)-13 increases miR-19a to compromise cyp27b1 (a vitamin D hydroxylase) in peripheral CD14 cells. Bone mineral density of L2-L4 was measured in 20 patients with ulcerative colitis (UC) and 20 healthy subjects. Peripheral CD14 cells were isolated from healthy people and patients with UC. Expression of cyp27b1 by CD14 cells was analyzed in the presence or absence of IL-13 in the culture. We observed that bone mineral density (BMD) in UC patients was significantly lower than healthy subjects. The BMD is negatively correlated with miR-19a in peripheral CD14 cells. MiR-19a in peripheral CD14 cell was correlated with serum IL-13 in UC patients. Expression of cyp27b1 in peripheral CD14 cells was correlated with miR-19a and serum IL-13 in UC patients. IL-13 suppressed cyp27b1 expression in CD14 cells. IL-13 increased expression of miR-19a in CD14 cells. IL-13 suppresses cyp27b1 expression in peripheral CD14 cells via up regulating miR-19a expression. J. Cell. Biochem. 118: 376-381, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Discussionsupporting

confidence: 86%

Interleukin-13 Inhibits Expression of cyp27b1 in Peripheral CD14+ Cells That Is Correlated With Vertebral Bone Mineral Density of Patients With Ulcerative Colitis

Ding

Zhou

et al. 2016

J. Cell. Biochem.

View full text Add to dashboard Cite

show abstract

“…Several in vitro and in vivo studies have high lighted the potential mechanism of action of these drugs. Ciclosporin A and tacrolimus bind to speci fic intra cellular receptors (immunophilins) and act by blocking the activation of the transcription factor nuclear fac tor of activated T cells (NFAT) that controls cytokine gene transcription and apoptosis resistance of lympho cytes 18,19 . Moreover, methotrexate affects survival of immune cells by blocking cell proliferation and indu cing apoptosis 20 .…”

Section: Classic Immunosuppressive Drugsmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

512

403

View full text Add to dashboard Cite

Inflammatory bowel diseases (including IBD, exempli fied by Crohn's disease and ulcerative colitis) are chronic relapsing disorders affecting the gastrointestinal tract. IBD has a progressive and destructive nature and, there fore, can cause various complications including steno ses, abscesses, fistulas, extraintestinal manifestations and colitis associated neoplasias and cancer 1,2 . Thus, effective therapeutic approaches are of high clinical rele vance in patients with IBD. This Review summarizes current therapeutic strategies and highlights emerging new treatment approaches for IBD with special refer ence to the proposed molecular mechanisms of action of anti inflammatory drugs. Current IBD therapiesClassic anti-inflammatory drugs. 5 Aminosalicylates (5 ASAs) are important anti inflammatory drugs that are frequently used for anti inflammatory therapy in patients with ulcerative colitis 3 . By contrast, 5 ASA based drugs show little or no efficacy in inducing res olution of clinical symptoms and tissue inflammation in patients with Crohn's disease 4 .5 ASAs are effective for induction and mainten ance of remission in ulcerative colitis and might also reduce the risk of developing colitis associated tumours in these patients 5 . Several mechanisms of action for 5 ASAs have been proposed, including reduction of prostaglandin synthesis via inhibition of cyclooxygenase, suppression of proinflammatory cytokine production and oxygen free radicals, inhib ition of lipoxygenase, blockade of neutrophil chemo taxis and mast cell activation, and impairment of nuclear factor κB activation (NF κB) in immune cells 3 . Moreover, studies in mice revealed that 5 ASA based drugs augment peroxisome proliferator activated receptor γ (PPARγ) expression and promote PPARγ translocation from the cytoplasm to the nucleus where they result in activation of peroxisome proliferator hormone response element driven genes to suppress colitis activity 6,7 .In addition to 5 ASAs, corticosteroids (systemically or topically delivered) have been used for remission induction in ulcerative colitis 2 . Although cortico steroids favour induction of remission in both ulcer ative colitis and Crohn's disease, they are not suitable for mainten ance of remission in IBD 1,2 . Mechanistically, gluco corticoids bind to a specific cytosolic receptor fol lowed by translocation of the complex to the nucleus to either activate or repress gene transcription (via bind ing to DNA corticosteroid response elements) 8,9 . Additionally, the glucocorticoid-receptor complex can inactivate pro inflammatory transcription factors such as NF κB and activator protein 1 (AP1) via proteinprotein inter actions, thereby preventing their activation of inflammatory mediators (for example, leukotrienes and cytokines such as IL 1 and IL 6). REVIEWS© 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

show abstract

“… 137 138 139 140 141 Cyclosporine-A and methotrexate suppress the secretion of pro-inflammatory cytokines and induce apoptosis. 142 143 144 145 Cyclosporine-A suppresses the production of IL-22 and TNF-α by NCR + ILC3. 146 …”

Section: Ibd Therapeuticsmentioning

confidence: 99%

Immunological pathogenesis of inflammatory bowel disease

2018

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17) cells and innate lymphoid cells (ILCs) are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

show abstract

Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

Cited by 14 publications

References 52 publications

Interleukin-13 Inhibits Expression of cyp27b1 in Peripheral CD14+ Cells That Is Correlated With Vertebral Bone Mineral Density of Patients With Ulcerative Colitis

Interleukin-13 Inhibits Expression of cyp27b1 in Peripheral CD14+ Cells That Is Correlated With Vertebral Bone Mineral Density of Patients With Ulcerative Colitis

Current and emerging therapeutic targets for IBD

Immunological pathogenesis of inflammatory bowel disease

Contact Info

Product

Resources

About