Abstract
Simple SummaryThe cytokine-activated Janus kinase (JAK)—signal transducer and activator of transcription (STAT) pathway has an important role in the regulation of immunity and inflammation. In addition, the signaling of this pathway has been reported to be associated with mammary gland development and milk production. Because of such important functions, the JAK-STAT pathway has been widely targeted in both human and animal diseases as a therapeutic agent. Recently, the JAK2, STATs, and inhibitors of the JAK-STAT pathway, especially cytokine signaling suppressors (SOCSs), have been reported to be associated with milk production and mastitis-resistance phenotypic traits in dairy cattle. Thus, in the current review, we attempt to overview the development of the JAK-STAT pathway role in bovine mastitis and milk production.The cytokine-activated Janus kinase (JAK)—signal transducer and activator of transcription (STAT) pathway is a sequence of communications between proteins in a cell, and it is associated with various processes such as cell division, apoptosis, mammary gland development, lactation, anti-inflammation, and immunity. The pathway is involved in transferring information from receptors on the cell surface to the cell nucleus, resulting in the regulation of genes through transcription. The Janus kinase 2 (JAK2), signal transducer and activator of transcription A and B (STAT5 A & B), STAT1, and cytokine signaling suppressor 3 (SOCS3) are the key members of the JAK-STAT pathway. Interestingly, prolactin (Prl) also uses the JAK-STAT pathway to regulate milk production traits in dairy cattle. The activation of JAK2 and STATs genes has a critical role in milk production and mastitis resistance. The upregulation of SOCS3 in bovine mammary epithelial cells inhibits the activation of JAK2 and STATs genes, which promotes mastitis development and reduces the lactational performance of dairy cattle. In the current review, we highlight the recent development in the knowledge of JAK-STAT, which will enhance our ability to devise therapeutic strategies for bovine mastitis control. Furthermore, the review also explores the role of the JAK-STAT pathway in the regulation of milk production in dairy cattle.
Highlights
Bovine mastitis is a seriously infectious and contagious disease, which is a massive threat to the dairy industry throughout the globe [1]
Janus kinase 2 (JAK2) plays a role as a bridge between STAT5A and prolactin receptor (PrlR), which is essential for milk production and mammary gland development
It can be concluded that a delicate equilibrium must be achieved for the effective activation of the Janus kinase (JAK)/STAT pathway, when the immune system is needed for action against infection, and proper restoration when the infection is diminished
Summary
Bovine mastitis is a seriously infectious and contagious disease, which is a massive threat to the dairy industry throughout the globe [1]. In Europe, collectively, the cost due to mastitis has reached 1.55 billion euros per year [10] This increased frequency was linked to public concerns for animal welfare and has made mastitis the key disease of the dairy sector [11]. Mammary epithelial cells are the first line of defense of the mammary gland to invading bacteria. They act as physical barriers and are capable of producing inflammatory mediators. Any disruption in the JAK-STAT pathway may lead to various diseases, including bovine mastitis that compromises the immune system of the host. JAK2 plays a role as a bridge between STAT5A and prolactin receptor (PrlR), which is essential for milk production and mammary gland development. Keeping in view the vital role of JAK-STAT signaling in immunity, inflammation, and milk production, the current review paper is designed with aims to summarize the role of the JAK-STAT pathway in bovine mastitis and milk production
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