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Received Jun 29, 2017; Revised Jan 3, 2018; Accepted Jan 11, 2018
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1. Introduction
Heme oxygenase (HO) catalyzes the oxidative degradation of heme to carbon monoxide (CO), iron, and biliverdin which is converted to bilirubin by biliverdin reductase [1]. HO-2 is constitutively expressed in the testes, brain, and endothelium and would regulate normal physiological functions while HO-1 is highly inducible by a wide range of stimuli. HO-1 plays an important role in the antioxidant defence system and iron homeostasis. In addition, HO-1 is involved in the regulation of different cell functions such as proliferation, differentiation, and apoptosis (reviewed in [2]). A wide range of evidence indicate that HO-1 regulates the activation and function of different cell types driving the inflammatory process and innate and adaptive immune responses [3–8]. Therefore, HO-1 upregulation or administration of its metabolites results in anti-inflammatory and antioxidant effects in many disease models such as atherosclerosis [9], cardiac ischemia/reperfusion injury [10], diabetes [11], inflammatory bowel disease [12], or rheumatoid arthritis [4]. Conversely, the deletion of Hmox1 in mice increases the severity of many experimental diseases, and the incidence or severity of several human diseases are associated with polymorphisms in the Hmox1 promoter that regulates HO-1 expression [7, 13].
HO-1 knockout (Hmox1−/−) mice exhibit growth retardation, anemia, proteinuria, hepatic and renal iron accumulation, chronic inflammation, and reduced life span [14], which are similar to the important alterations observed in human HO-1 deficiency [15, 16]. Conditional deletion of HO-1 could allow a more specific approach to study the role of HO-1 in physiological and pathological processes. Previous works have shown that mice with selective deletion of myeloid HO-1 (HO-1M-KO) do not exhibit any relevant physiologic changes compared with wild-type animals, and unlike HO-1−/− mice, they do not have enlarged spleens or pathological abnormalities [17].
A great number of studies have been devoted to assess HO-1 biological effects, in contrast with the relatively few investigations using targeted approaches to specifically focus on myeloid HO-1. Previous reports have indicated that myeloid HO-1 may be a protective pathway against renal ischemia/reperfusion...