Altered expression of MUC2 and MUC5AC in response to Shigella infection, an in vivo study Prakash Radhakrishnan a , Devaraj Halagowder b , S. Niranjali Devaraj a, ⁎ a Department of Biochemistry, University of Madras, Guindy Campus, Chennai-600 025, India b Department of Zoology (Unit of Biochemistry), University of Madras, Guindy Campus, Chennai, India Received 4 August 2006; received in revised form 21 December 2006; accepted 24 January 2007 Available online 23 February 2007 Abstract Infection of mucosal epithelial cells by Shigella species leads to an intense and acute inflammatory bowel disease that is characterized by watery diarrhea and purulent discharge. Mucin production is a common defense mechanism to protect the underlying mucosa against pathogens. The molecular mechanism(s) underlying mucin induction is unknown in Shigellosis. In this study, we have evaluated the relationship between Shigella infection, the expression of MUC2 and MUC5AC and the participation of signaling molecules TNF-α, PKC and ERK1/2. Shigella infection up-regulated MUC2 and MUC5AC expression in 6–8 h, through activation of TNF-α, PKC and ERK1/2. These results confirm that, in response to Shigella infection, the normal expression pattern of MUC-2 and MUC-5AC is altered. This in vivo study brings new insights into the molecular pathogenesis of Shigellosis and new potential therapeutic targets for Shigellosis. © 2007 Elsevier B.V. All rights reserved. Keywords: Shigella species; MUC2; MUC5AC; Ileal loop ligation assay; Shigellosis 1. Introduction Infectious diseases kill about 11 million children each year, and of the 11 million deaths, acute diarrheal diseases account for 3.2 million deaths in children less than 5 years of age. 600,000 of the 3.2 million deaths annually are contributed by shigellosis with 80% of the deaths occurring in the first 2 years of life [1]. Bacillary dysentery, the severest form of which is called Shigellosis, is caused by Shigella bacilli which bind and cross the mucus barrier that covers the intestinal epithelium before invading the mucosal epithelial cell [2]. The most common Shigella species causing shigellosis in the developing countries are Shigella flexneri and Shigella dysenteriae 1. S. flexneri is responsible for the endemic form of the disease, whereas S. dysenteriae accounts for the epidemic form of the disease. Industrialized areas are dominated by Shi- gella sonnei but Shigella boydii is rarely encountered and seems essentially associated with cases of shigellosis in the Indian subcontinent [3]. Shigella infection is a common intestinal problem that is usually self-limiting but it can become life threatening in infants as a result of dehydration or chronic malnutrition [4] and also in immunocompromised individuals because of their inability to combat the infection [5]. Adhesion of enteric pathogens to the mucosa of the gastrointestinal tract was recognized as an important early event in the colonization and development of diarrheal diseases [6]. Hence, the infectious diarrheal disease must be controlled to improve the life expectancy and quality of life for the children. Mucins have been reported to be pivotal to maintaining epithelium homeostasis in inflammatory diseases and cancer. The major component of mucus is mucin, a heavily glycosy- lated glycoprotein. Mucins protect, lubricate the epithelial surface and trap particles, including bacteria and viruses, for mucociliary clearance. To date, 20 mucin genes (MUC) have been identified and noted as MUC1–2, MUC3A, MUC3B, MUC4, MUC5AC, MUC5B,MUC6–13, MUC15–17, and MUC19–20 and they are observed as O-linked glycoproteins expressed either at the cell surface or as secreted molecules to Biochimica et Biophysica Acta 1770 (2007) 884 – 889 www.elsevier.com/locate/bbagen ⁎ Corresponding author. Tel.: +91 44 24419596; fax: +91 44 22352494. E-mail addresses: niranjali@yahoo.com, rpmucin@yahoo.co.in (S.N. Devaraj). 0304-4165/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.bbagen.2007.01.019