PMID- 23897745 OWN - NLM STAT- MEDLINE DCOM- 20161031 LR - 20161230 IS - 1932-7005 (Electronic) IS - 1932-6254 (Linking) VI - 10 IP - 2 DP - 2016 Feb TI - The essential role of annexin A1 mimetic peptide in the skin allograft survival. PG - E44-53 LID - 10.1002/term.1773 [doi] AB - Immunosuppressive drugs have a critical role in inhibiting tissue damage and allograft rejection. Studies have demonstrated the anti-inflammatory effects of the annexin A1 (AnxA1) in the regulation of transmigration and apoptosis of leucocytes. In the present study, an experimental skin allograft model was used to evaluate a potential protective effect of AnxA1 in transplantation survival. Mice were used for the skin allograft model and pharmacological treatments were carried out using either the AnxA1 mimetic peptide Ac2-26, with or without cyclosporine A (CsA), starting 3 days before surgery until rejection. Graft survival, skin histopathology, leucocyte transmigration and expression of AnxA1 and AnxA5 post-transplantation were analysed. Pharmacological treatment with Ac2-26 increased skin allograft survival related with inhibition of neutrophil transmigration and induction of apoptosis, thereby reducing the tissue damage compared with control animals. Moreover, AnxA1 and AnxA5 expression increased after Ac2-26 treatment in neutrophils. Interestingly, the combination of Ac2-26 and cyclosporine A showed similar survival of transplants when compared with the cyclosporine A group, which could be attributed to a synergistic effect of both drugs. Investigations in vitro revealed that cyclosporine A inhibited extracellular-signal-regulated kinase (ERK) phosphorylation induced by Ac2-26 in neutrophils. Overall, the results suggest that AnxA1 has an essential role in augmenting the survival of skin allograft, mainly owing to inhibition of neutrophil transmigration and enhancement of apoptosis. This effect may lead to the development of new therapeutic approaches relevant to transplant rejection. CI - Copyright (c) 2013 John Wiley & Sons, Ltd. FAU - Teixeira, Rodrigo Antonio Parra AU - Teixeira RA AD - Post-Graduation in Structural and Functional Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Mimura, Kallyne Kioko Oliveira AU - Mimura KK AD - Post-Graduation in Structural and Functional Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Araujo, Leandro Pires AU - Araujo LP AD - Post-Graduation in Structural and Functional Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Greco, Karin Vicente AU - Greco KV AD - Department of Surgical Research, Northwick Park Institute for Medical Research - University College London, London, UK. FAU - Oliani, Sonia Maria AU - Oliani SM AD - Post-Graduation in Structural and Functional Biology, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil. AD - Department of Biology, Instituto de Biociencias, Letras e Ciencias Exatas (IBILCE), Sao Paulo State University (UNESP), Sao Jose do Rio Preto, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130730 PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Annexin A1) RN - 0 (Annexin A5) RN - 0 (Peptides) RN - 0 (Protective Agents) RN - 0 (annexin A1 peptide (2-26)) RN - 83HN0GTJ6D (Cyclosporine) RN - AYI8EX34EU (Creatinine) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Allografts/*drug effects MH - Animals MH - Annexin A1/*pharmacology MH - Annexin A5/metabolism MH - Apoptosis/drug effects MH - Cell Movement/drug effects MH - Creatinine/urine MH - Cyclosporine/pharmacology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Graft Survival/*drug effects MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Neutrophils/cytology/drug effects MH - Peptides/*pharmacology MH - Phosphorylation/drug effects MH - Protective Agents/pharmacology MH - *Skin Transplantation OTO - NOTNLM OT - annexin A1 OT - cyclosporine A OT - neutrophils OT - skin OT - transplantation EDAT- 2013/07/31 06:00 MHDA- 2016/11/01 06:00 CRDT- 2013/07/31 06:00 PHST- 2012/10/04 00:00 [received] PHST- 2013/04/15 00:00 [revised] PHST- 2012/04/16 00:00 [accepted] PHST- 2013/07/31 06:00 [entrez] PHST- 2013/07/31 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] AID - 10.1002/term.1773 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2016 Feb;10(2):E44-53. doi: 10.1002/term.1773. Epub 2013 Jul 30.