Lack of TNFRI signaling enhances annexin A1 biological activity in intestinal inflammation

Sena, Angela A.; Pedrotti, L.; Barrios, Bibiana E.; Cejas, Hugo; Balderramo, Domingo; Diller, Ana; Correa, Silvia G.

doi:10.1016/j.bcp.2015.09.009

Cited by 22 publications

(27 citation statements)

References 47 publications

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“…Moreover, the relevance of neutrophils in colitis is reinforced by the fact that IFX treatment reduced DSS effects in WT mice, but did not reduce neutrophil influx. This observation corroborates similar neutrophil influx in WT and tumor necrosis factor receptor 1 knockout mice (TNFR1 À/À ) in DSS induced colitis [14].…”

Section: Discussionsupporting

confidence: 81%

“…The systemic up-regulation of transcriptional expression and release of plasma AnxA1 was correlated with improved quality of life in these patients [13]. Further data demonstrated that biopsies from healthy volunteers and patients undergoing anti-TNF-a therapy with remittent UC, presented with higher AnxA1 expression than those with the active disease [14]. Together, our results demonstrate that AnxA1 is a potential key protein in anti-TNF-a therapy.…”

Section: Introductionmentioning

confidence: 62%

“…Colitis was induced by Dextran Sulfate Sodium (DSS, MW 40,000, Dextran Products Limited, Canada), at a concentration of 5% in sterilized drinking water [14]. Fresh DSS solution was replenished every two days (days 0, 2 and 4).…”

Section: Colitis Induction and Clinical Analysismentioning

confidence: 99%

“…Neutrophil infiltration was indirectly assessed by myeloperoxidase (MPO) measurement as previously described [14]. Briefly, fragments of the middle colon were weighted to a correct calculation for the concentration.…”

Section: Myeloperoxidase Measurementmentioning

confidence: 99%

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Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis

Paula-Silva

Barrios

Maccio-Maretto

et al. 2016

Biochemical Pharmacology

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TNF-α is involved in the mechanisms that initiate inflammatory bowel diseases (IBDs). Anti-TNF-α drugs, such as infliximab (IFX), cause non-responsiveness and side effects, indicating the need to investigate alternative therapies for these diseases. The anti-inflammatory protein, annexin A1 (AnxA1), has been associated with the protection of the gastrointestinal mucosa. To further address the role of endogenous AnxA1 on the TNF-α blockade efficacy in a murine model, we assessed colitis induced by Dextran Sulfate Sodium (DSS) in wild-type (WT) and AnxA1(-/-) Balb/c mice treated with IFX. We consistently observed endogenous AnxA1 prevented clinical and physiological manifestations of experimental colitis treated with IFX, additionally the manifestation of the disease was observed earlier in AnxA1(-)(/-) mice. Rectal bleeding, diarrhea, histological score, epithelial damages and collagen degradation caused by DSS were prevented following IFX treatment only in WT mice. IL-6 increased during colitis in WT and AnxA1(-)(/-) mice, decreasing under IFX treatment in WT. The influx of neutrophils and TNF-α secretion were largely elevated in AnxA1(-)(/-) mice when compared to WT mice. In the group WT/DSS+IFX, phagocytes were more susceptible to apoptosis following treatment with IFX. Endogenous expression of AnxA1 increased after DSS and decreased with IFX treatment, demonstrating an attenuated inflammatory response. The data indicate that AnxA1 contributes to the establishment of intestinal homeostasis after blocking of TNF-α was used as a treatment of IBD, constituting a key molecule in the mechanism of action and a potential biomarker of therapeutic efficacy.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 62%

Section: Colitis Induction and Clinical Analysismentioning

confidence: 99%

Section: Myeloperoxidase Measurementmentioning

confidence: 99%

See 2 more Smart Citations

Role of the protein annexin A1 on the efficacy of anti-TNF treatment in a murine model of acute colitis

Paula-Silva

Barrios

Maccio-Maretto

et al. 2016

Biochemical Pharmacology

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show abstract

“…Furthermore, biopsies from UC patients with anti-TNF-α therapy during disease remission revealed increased mucosal ANXA1 protein. Additionally, TNF- α inhibition increased ANXA1 expression in the intestinal epithelium and promoted resolution of inflammation in a murine colitis model (Sena et al , 2015). Interestingly, ANXA1 knockout mice have increased susceptibility to Dextran Sulfate Sodium (DSS) – induced colitis and delayed recovery from colitis (Leoni et al , 2013).…”

Section: Annexin A1 As a Potential Therapeutic Tool To Reduce Mucosalmentioning

confidence: 99%