Carbon monoxide exposure improves immune function in lupus‐prone mice

Mackern-Oberti, Juan Pablo; Llanos, Carolina; Carreño, Leandro J.; Riquelme, Sebastián A.; Jacobelli, S; Anegón, Ignacio; Kalergis, Alexis M.

doi:10.1111/imm.12124

Cited by 37 publications

(39 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other groups have also confirmed these findings. In a recent study on lupus-prone mice, HO-1 induction and CO exposure improved the symptoms of the disease [137]. In a pilot study on 90 patients, each 1 µmol/l increase in serum bilirubin was associated with 15% odds for the occurrence of Crohn's disease [138] while in a genomic study of patients with Crohn's disease, a homozygous state of UGT1A1*28 associated with higher bilirubin rendered protection against the disease [131].…”

Section: Bilirubin In Immunological Disordersmentioning

confidence: 96%

The pharmacological features of bilirubin: the question of the century

Zahir

Rabbani

Khan

et al. 2015

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

This review looks at the toxicity and metabolism of bilirubin in terms of its pharmacological potential. Its role has gained importance as more research has revealed the functional significance and interrelationship between the gasotransmitters nitric oxide and carbon monoxide. The biological actions of bilirubin have mostly been characterized in the high micromolar range where toxic effects occur. However, it could also prove to be an important cytoprotector for brain tissue, which is inherently less equipped for antioxidant defense. Plasma bilirubin levels negatively correlate to a number of disease states. Higher levels of bilirubin that are still within the normal range provide a protective effect to the body. The effects on various disorders could be tested using controlled pharmacological upregulation of the molecule with animal models. At nanomolar concentrations, considerable benefits have been obtained when the molecule was delivered pharmacologically under in vitro or in vivo test conditions, particularly in neurodegenerative disorders and after tissue or organ transplantation. The induction of heme oxygenase-1 (HMOX-1) via the activation of nuclear factor erythroid 2-related factor or the use of bile pigments in the harvesting of diseased tissue are novel applications, and like every new therapy, should be used with caution. HMOX-1 is tissue specific, and in exceptional states, such as schizophrenia and specific types of renal disorder, the same therapy may have disastrous effects.

show abstract

Section: Bilirubin In Immunological Disordersmentioning

confidence: 96%

The pharmacological features of bilirubin: the question of the century

Zahir

Rabbani

Khan

et al. 2015

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

show abstract

“…Haem‐oxygenase 1 is constitutively expressed by DCs and can be up‐regulated after PAMPs stimulation . However, HO‐1 over‐expression is not observed at early times during maturation.…”

Section: The Ho‐1–co System As a Modulator Of Antigen Presentation Bymentioning

confidence: 99%

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

et al. 2016

Self Cite

View full text Add to dashboard Cite

SummaryHaem-oxygenase-1 (HO-1) is an enzyme responsible for the degradation of haem that can suppress inflammation, through the production of carbon monoxide (CO). It has been shown in several experimental models that genetic and pharmacological induction of HO-1, as well as non-toxic administration of CO, can reduce inflammatory diseases, such as endotoxic shock, type 1 diabetes and graft rejection. Recently, it was shown that the HO-1/CO system can alter the function of antigen-presenting cells (APCs) and reduce T-cell priming, which can be beneficial during immune-driven inflammatory diseases. The molecular mechanisms by which the HO-1 and CO reduce both APC-and T-cell-driven immunity are just beginning to be elucidated. In this article we discuss recent findings related to the immune regulatory capacity of HO-1 and CO at the level of recognition of pathogen-associated molecular patterns and T-cell priming by APCs. Finally, we propose a possible regulatory role for HO-1 and CO over the recently described mitochondria-dependent immunity. These concepts could contribute to the design of new therapeutic tools for inflammation-based diseases.

show abstract

“…HO-1 deficiency is associated with an increased susceptibility to uncontrolled inflammation with subsequent leucocytosis, splenomegaly and lymph node swelling in affected individuals [12,13]. Furthermore, we have described recently that both SLE patients, as well as lupus-prone mice, show a decreased expression of HO-1 in peripheral blood monocytes [14,15]. During immune-mediated diseases, such as MS, type 1 diabetes, collagen induced arthritis (CIA) and organ transplant rejection, several immunoregulatory functions have been attributed to CO, which is an HO-1 product [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

“…All animal work was performed according to institutional guidelines and supervised by a veterinarian. Mice were exposed to compressed CO at a concentration of 250 parts per million (ppm) for 2 h per day from weeks 9 to 15-30 [15] (at week 15, n mice /group 5 5, three independent experiments; at week 30, n mice /group 5 5, two independent experiments). A CO analyser was used to measure and keep controlled gas concentration in chambers.…”

Section: Introductionmentioning

confidence: 99%

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

Mackern-Oberti

Obreque

Méndez

et al. 2015

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummarySystemic lupus erythematosus is characterized by the presence of circulating anti-nuclear antibodies (ANA) and systemic damage that includes nephritis, haematological manifestations and pulmonary compromise, among others. Although major progress has been made in elucidating the molecular mechanisms responsible for autoimmunity, current therapies for lupus have not improved considerably. Because the exposure of carbon monoxide (CO) has been shown to display beneficial immunoregulatory properties in different immune-mediated diseases, we investigated whether CO therapy improves lupus-related kidney injury in lupus mice. MRL-Fas lpr lupus mice were exposed to CO and disease progression was evaluated. ANA, leucocyteinfiltrating populations in spleen, kidney and lung and kidney lesions, were measured. CO therapy significantly decreased the frequency of activated B220 1 CD4 2 CD8 2 T cells in kidneys and lungs, as well as serum levels of ANA. Furthermore, we observed that CO therapy reduced kidney injury by decreasing proliferative glomerular damage and immune complexes deposition, decreased proinflammatory cytokine production and finally delayed the impairment of kidney function. CO exposure ameliorates kidney and lung leucocyte infiltration and delays kidney disease in MRLFas lpr lupus mice. Our data support the notion that CO could be explored as a potential new therapy for lupus nephritis.

show abstract

Carbon monoxide exposure improves immune function in lupus‐prone mice

Cited by 37 publications

References 51 publications

The pharmacological features of bilirubin: the question of the century

The pharmacological features of bilirubin: the question of the century

Modulation of antigen processing by haem‐oxygenase 1. Implications on inflammation and tolerance

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

Contact Info

Product

Resources

About