Abstract
Heme oxygenase-1 (HO-1) is induced by many stimuli to modulate the activation and function of different cell types during innate immune responses. Although HO-1 has shown anti-inflammatory effects in different systems, there are few data on the contribution of myeloid HO-1 and its role in inflammatory processes is not well understood. To address this point, we have used HO-1M-KO mice with myeloid-restricted deletion of HO-1 to specifically investigate its influence on the acute inflammatory response to zymosan in vivo. In the mouse air pouch model, we have shown an exacerbated inflammation in HO-1M-KO mice with increased neutrophil infiltration accompanied by high levels of inflammatory mediators such as interleukin-1β, tumor necrosis factor-α, and prostaglandin E2. The expression of the degradative enzyme matrix metalloproteinase-3 (MMP-3) was also enhanced. In addition, we observed higher levels of serum MMP-3 in HO-1M-KO mice compared with control mice, suggesting the presence of systemic inflammation. Altogether, these findings demonstrate that myeloid HO-1 plays an anti-inflammatory role in the acute response to zymosan in vivo and suggest the interest of this target to regulate inflammatory processes.
Highlights
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]
Heme oxygenase-1 (HO-1) expression was observed in macrophages from Hmox1FL/FL but not in LysMCre/+Hmox1FL/FL (HO-1M-KO) mice, confirming the efficient deletion of myeloid HO-1
We have shown that HO-1M-KO mice exhibit increased neutrophil infiltrates in response to zymosan administration
Summary
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. 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 [3,4,5,6,7,8]. The deletion of Hmox in mice increases the severity of many experimental diseases, and the incidence or severity of several human diseases are associated with polymorphisms in the Hmox promoter that regulates HO-1 expression [7, 13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
