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About the Authors:
Pedro L. Vera
* E-mail: [email protected]
Affiliations Bay Pines VA Healthcare System, Research & Development (151), Bay Pines, Florida, United States of America, Department of Surgery, College of Medicine, University of South Florida, Tampa, Florida, United States of America
Kenneth A. Iczkowski
Affiliation: Prostate Cancer Research Laboratories, University of Colorado-Denver, Aurora, Colorado, United States of America
Xihai Wang
Affiliations Bay Pines VA Healthcare System, Research & Development (151), Bay Pines, Florida, United States of America, Department of Surgery, College of Medicine, University of South Florida, Tampa, Florida, United States of America
Katherine L. Meyer-Siegler
Affiliations Bay Pines VA Healthcare System, Research & Development (151), Bay Pines, Florida, United States of America, Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, Florida, United States of America
Introduction
Macrophage migration inhibitory factor (MIF) is an ubiquitous pleiotropic cytokine involved in cell proliferation and inflammation [1], [2]. MIF plays an important and unique role in inflammation since MIF stands upstream of other pro-inflammatory mediators and it can counter-regulate the anti-inflammatory effects of glucocorticoids [2]. MIF is implicated in animal models of inflammatory diseases, including arthritis, glomerulonephritis, acute lung injury and sepsis (for recent review [3]).
Our recent experimental evidence indicates that MIF participates in bladder inflammation since: (1) MIF is constitutively expressed in the urothelium [4], [5]; (2) bladder MIF expression is upregulated in different models of experimental cystitis in animals [6], [7]; (3) MIF is released from the bladder during experimental cystitis [6], [8], [9] and urinary tract infections in humans [10] and finally, (4) neutralizing MIF with intravesical antibodies decreased experimental bladder inflammation [7]. Thus, based on our experimental observations, our hypothesis of a pro-inflammatory role for MIF during bladder inflammation agrees well with MIF's pro-inflammatory role in several disease models (e.g. arthritis, Crohn's disease) where treatment with neutralizing MIF antibodies results in decreased inflammation [11], [12].
The mechanism for MIF's action is not completely defined and remains an active area of investigation. MIF may exert autocrine effects through binding to intracellular JAB1 [13] and also paracrine effects by binding to cell-surface receptors [14]. Until recently, complex formation between MIF and cell-surface CD74 was the only described mechanism for MIF-receptor interaction [15] . CD74 is part of the major histocompatibility...