Contents lists available at ScienceDirect Microbial Pathogenesis journal homepage: www.elsevier.com/locate/micpath NFκB transcription factor (p65) immunohistochemistry in leprosy dermal microvasculature Luciana Mota Silva a , Kelly Emi Hirai a , Jorge Rodrigues de Sousa b , Juarez de Souza a , Leônidas Braga Dias Jr. a , Francisca Regina Oliveira Carneiro a , Tinara Leila de Souza Aarão a , Hellen Thais Fuzii b , Juarez Antonio Simões Quaresma a,b,∗ a Center of Biological and Health Science, State University of Para, Belem, Brazil b Tropical Medicine Center, Federal do Para University, Belem, Brazil ARTICLE INFO Keywords: Leprosy Endothelial adhesion molecules NFκB ABSTRACT Leprosy caused by Mycobacterium leprae is characterized by a spectrum of clinical manifestations that are de- termined by the predominant immunological profile of the host. The recruitment of leukocytes to the sites of injury can influence the development of these profiles. Cell adhesion molecules such as ICAM-1, VCAM-1 and CD62E participate in this process and their expression is regulated by transcriptions factors such as NFκB. To correlate the expression of cell adhesion molecules and NFκB (p65) in leprosy lesions, 30 skin biopsies of patients with leprosy [16 with the tuberculoid (TT) or borderline tuberculoid (BT) forms and 14 with the lepromatous (LL) or borderline lepromatous (BL) forms] were analyzed by immunohistochemistry. A larger mean number of cells expressing VCAM-1 (BT/TT: 18.28 ± 1.4; BL/LL: 10.67 ± 1.2; p = 0.0002), ICAM-1 (BT/TT: 9.92 ± 1.1; BL/LL: 5.87 ± 1.0; p = 0.0084) and CD62E (BT/TT: 13.0 ± 1.5; BL/LL: 2.58 ± 0.3; p = 0.0001) were observed in BT and TT lesions. The mean number of cells expressing NFκB was similar in the two clinical forms (BT/TT: 2.21 ± 2.7; BL/LL: 2.35 ± 3.1;p = 0.9285). No significant correlation was observed between expression of the transcription factor and adhesion molecules analyzed. The synthesis of ICAM-1, VCAM-1 and CD62E depends on the activation of NFκB, which acts synergistically with other transcription factors. Adequate activation of intracellular signaling pathways results in the production of endothelial adhesion molecules, contributing to the recruitment of cells to the site of injury and thus eliciting an effective inflammatory response in the elimination of the bacillus. 1. Introduction Leprosy is a chronic infectious disease caused by the obligate in- tracellular parasite Mycobacterium leprae. The interaction between the bacillus and human immune system determines the clinical manifes- tations of the disease [1]. These manifestations vary from a localized, resistant form in which a Th1 immune profile predominates, called tuberculoid-tuberculoid (TT), to the opposite form, called lepromatous- lepromatous (LL), characterized by disseminated infection and the predominance of a Th2 profile. Borderline forms [borderline-tubercu- loid (BT), borderline-borderline (BB), and borderline-lepromatous (BL)] exist between these two forms whose immunological and clinical characteristics oscillate between the two poles [2]. The recruitment of blood leukocytes to the site of injury is of fun- damental importance for the development of an adequate inflammatory response [3]. This process starts with leukocyte rolling in which leukocytes roll on selectins expressed on activated endothelial cells. The step of firm adhesion is mediated by integrins whose ligands are members of the immunoglobulin family, including intercellular adhe- sion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), which are expressed on the surface of endothelial cells [4]. The firm adhesion of leukocytes to endothelial cells is followed by transmigration [3]. Transcription factor NFκB regulates the expression of inflammatory genes involved in the pathogenesis of inflammatory and infectious diseases, including leukocyte-endothelial adhesion molecules [5]. In the cytoplasm of unstimulated cells, NFκB is bound to an inhibitor, called IκB, which retains it in an inactivated state and prevents its migration to the nucleus. Once stimulated, IκB is degraded, releasing NFκB that can translocate to the nucleus and promote gene transcrip- tion [6]. The expression of some leukocyte-endothelial adhesion molecules is https://doi.org/10.1016/j.micpath.2017.11.027 Received 16 September 2017; Received in revised form 11 November 2017; Accepted 18 November 2017 ∗ Corresponding author. Núcleo de Medicina Tropical, UFPA, Av. Generalíssimo Deodoro 92, Umarizal, Belem, Para, 66055-190, Brazil. E-mail address: juarez@pesquisador.cnpq.br (J.A.S. Quaresma). Microbial Pathogenesis 113 (2017) 427–431 Available online 21 November 2017 0882-4010/ © 2017 Elsevier Ltd. All rights reserved. T