Sains Malaysiana 50(1)(2021): 207-226

http://dx.doi.org/10.17576/jsm-2021-5001-21

Annexin A1 (ANXA1): A Systematic Review of Its Role in Inflammation

(Aneksin A1 (ANXA1): Suatu Ulasan Sistematik tentang Peranannya dalam Keradangan)

SANGGAVI NADARAJAN, NORAZRINA AZMI, MALINA JASAMAI & ENDANG KUMOLOSASI*

Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Federal Territory, Malaysia

Received: 23 April 2020/Accepted: 1 July 2020

ABSTRACT

Inflammation is a body response towards any injury or tissue damage. It involves the accumulation of neutrophils and release of inflammatory mediators. ANXA1, a 37 kDa glucocorticoid inducible protein plays an important role in resolving inflammation. The unique N-terminal and its mimetic peptide exert strong anti-inflammatory actions. This study was conducted to review the roles of ANXA1 in inflammation and identify any other reported roles. Electronic search was done whereby a total of 3797 articles were located from three databases, namely Ovid MEDLINE, Science Direct, and PubMed. Articles on ANXA1 and inflammation were selected based on inclusive criteria and review papers were excluded. Bias analysis was performed based on bias risk tool and 27 articles were included in the study. It was found that ANXA1 was able to resolve inflammation in many inflammatory diseases. Upon treatment with glucocorticoid, ANXA1 is induced and its significant expressions in tissues are important in resolving inflammation. However, this effect can be reversed by administering an anti-annexin antibody. This protein also acts on members of all formyl peptide receptors (FPR) and activates them to initiate reaction. It acts mainly by causing the death of neutrophils through apoptosis. In addition, ANXA1 is identified as a marker in cancer cells which determines the survival rates. In conclusion, ANXA1 is a key modulator in resolving inflammation in many diseases and is actively being induced upon glucocorticoid treatment.

Keywords: Annexin A1; Annexin 1; ANXA1; inflammation; Lipocortin-1; phospholipase A2 inhibitory protein

ABSTRAK

Keradangan adalah tindak balas badan terhadap sebarang kecederaan atau kerosakan tisu. Ia melibatkan pengumpulan neutrofil dan pembebasan perantara keradangan. ANXA1, sejenis protein yang boleh diaruh glukokortikoid 37 kDa memainkan peranan penting dalam menangani keradangan. Terminal-N yang unik dan peptida mimetiknya menunjukkan tindakan anti-keradangan yang kuat. Kajian ini dijalankan untuk mengkaji peranan ANXA1 dalam keradangan dan mengenal pasti lain-lain peranan yang dilaporkan. Pencarian elektronik dilakukan dan sejumlah 3797 artikel diperoleh daripada tiga pangkalan data iaitu Ovid MEDLINE, Science Direct dan PubMed. Artikel mengenai ANXA1 dan keradangan dipilih berdasarkan kriteria inklusif dan tidak termasuk artikel ulasan. Analisis pincang dilakukan berdasarkan peralatan risiko pincang dan 27 artikel dimasukkan dalam kajian. Didapati bahawa ANXA1 dapat menangani keradangan dalam pelbagai penyakit radang. Semasa rawatan menggunakan glukokortikoid, ANXA1 diaruh dan ekspresi ketaranya dalam tisu adalah penting dalam menangani keradangan. Walau bagaimanapun, kesan ini dapat dibalikkan dengan menggunakan antibodi anti-aneksin. Protein ini juga didapati bertindak pada semua jenis reseptor peptida formil (FPR) dan mengaktifkannya untuk memulakan tindak balas. Ia bertindak terutamanya dengan menyebabkan kematian neutrofil melalui apoptosis. Sebagai tambahan, ANXA1 dikenal pasti sebagai penanda sel barah yang menentukan kadar kemandirian. Kesimpulannya, ANXA1 adalah modulator utama dalam menangani keradangan dalam pelbagai penyakit dan secara aktif diaruh oleh rawatan glukokortikoid.

Kata kunci: Aneksin A1; Aneksin 1; ANXA1; keradangan; Lipokortin-1; protein penyekat fosfolipase A2

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*Corresponding author; email: e_kumolosasi@ukm.edu.my