Cholesterol-25-hydroxylase promotes efferocytosis and resolution of lung inflammation

Madenspacher, Jennifer H.; Morrell, Eric D.; Gowdy, Kymberly M.; McDonald, Jeffrey G.; Thompson, Bonne M.; Muse, Ginger W.; Martinez, Jennifer; Thomas, Seddon Y.; Mikacenic, Carmen; Nick, Jerry A.; Abraham, Edward; Garantziotis, Stavros; Stapleton, Renee D.; Meacham, Julie; Thomassen, Mary Jane; Janssen, William J.; Cook, Donald N.; Wurfel, Mark M.; Fessler, Michael B.

doi:10.1172/jci.insight.137189

Cited by 47 publications

(78 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several hypotheses could be considered to explain the differences observed in these two compartments. For instance, 25‐OHC was shown to be involved in the efferocytosis of apoptotic neutrophils by alveolar macrophages and thus decreased neutrophilia and lung inflammation 46 . This effect on efferocytosis could be implicated in the beneficial effects we observed with 25‐OHC in the ALI model.…”

Section: Discussionmentioning

confidence: 74%

25‐Hydroxycholesterol metabolism is altered by lung inflammation, and its local administration modulates lung inflammation in mice

et al. 2021

View full text Add to dashboard Cite

Inflammation is a critical component of many lung diseases including asthma and acute lung injury (ALI). Using high‐performance liquid chromatography–mass spectrometry, we quantified the levels of oxysterols in two different murine models of lung diseases. These are lipid mediators derived from cholesterol and known to modulate immunity and inflammation. Interestingly, 25‐hydroxycholesterol (25‐OHC) was the only oxysterol with altered levels during lung inflammation, and its levels were differently affected according to the model. Therefore, we sought to assess how this oxysterol would affect lung inflammatory responses. In a model of lipopolysaccharide (LPS)‐induced acute lung inflammation, 25‐OHC levels were increased, and most of the hallmarks of the model (eg, leukocyte recruitment, mRNA expression, and secretion of inflammatory cytokines) were decreased following its intratracheal administration. We also found that, when administered in the lung, 25‐OHC is metabolized locally into 25‐hydroxycholesterol‐3‐sulfate and 7α,25‐dihydroxycholesterol. Their administration in the lungs did not recapitulate all the effects of 25‐OHC. Conversely, in a model of allergic asthma induced by intranasal administration of house dust mites (HDM), 25‐OHC levels were decreased, and when intranasally administered, this oxysterol worsened the hallmarks of the model (eg, leukocyte recruitment, tissue remodeling [epithelium thickening and peribranchial fibrosis], and cytokine expression) and induced changes in leukotriene levels. Ex vivo, we found that 25‐OHC decreases LPS‐induced primary alveolar macrophage activation while having no effect on neutrophil activation. Its sulfated metabolite, 25‐hydroxycholesterol‐3‐sulfate, decreased neutrophil, but not macrophage activation. Taken together, our data support a differential role of 25‐OHC in ALI and allergic inflammation models.

show abstract

Section: Discussionmentioning

confidence: 74%

25‐Hydroxycholesterol metabolism is altered by lung inflammation, and its local administration modulates lung inflammation in mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Although the mechanisms for this pro-inflammatory role of 25-HC are not understood, it has been recently reported that, by binding directly to surface integrins and activating their downstream signalling, 25-HC can promote the production of inflammatory cytokines [81]. More recently, 25-HC has also been shown to have anti-inflammatory roles, for instance, 25-HC produced by alveolar macrophages promotes lung homeostasis by inducing LXR-dependent resolution of neutrophilia [82]. Finally, it has been shown that 25-HC can be detected in plasma, where normal levels have been quantified as ∼5 ng/ml in humans [70,83] and can significantly increase upon TLR stimulation, to 10 ng/ml in healthy volunteers [70] and up to 200 ng/ml in mouse [84].…”

Section: Macrophagesmentioning

confidence: 99%

Cholesterol metabolism: a new molecular switch to control inflammation

Cardoso

Perucha

2021

Clinical Science

View full text Add to dashboard Cite

The immune system protects the body against harm by inducing inflammation. During the immune response, cells of the immune system get activated, divided and differentiated in order to eliminate the danger signal. This process relies on the metabolic reprogramming of both catabolic and anabolic pathways not only to produce energy in the form of ATP but also to generate metabolites that exert key functions in controlling the response. Equally important to mounting an appropriate effector response is the process of immune resolution, as uncontrolled inflammation is implicated in the pathogenesis of many human diseases, including allergy, chronic inflammation and cancer. In this review, we aim to introduce the reader to the field of cholesterol immunometabolism and discuss how both metabolites arising from the pathway and cholesterol homeostasis are able to impact innate and adaptive immune cells, staging cholesterol homeostasis at the centre of an adequate immune response. We also review evidence that demonstrates the clear impact that cholesterol metabolism has in both the induction and the resolution of the inflammatory response. Finally, we propose that emerging data in this field not only increase our understanding of immunometabolism but also provide new tools for monitoring and intervening in human diseases, where controlling and/or modifying inflammation is desirable.

show abstract

“…25-hydroksycholesterol może przeciwdziałać replikacji białek wirusowych w komórkach w hodowli in vitro. W chorobach infekcyjnych, wirusowych obserwuje się zmianę poziomu oksysteroli we krwi pacjentów [66].…”

Section: Oksysterole W Stanach Zapalnych I Infekcjach Wirusowychunclassified

Od glejaka po COVID-19 - rola oksysteroli w organizmie człowieka

Gonet-Surówka¹,

Dynarowicz-Łątka²

2021

Postepy Biochem

View full text Add to dashboard Cite

Cholesterol jest prekursorem w syntezie witaminy D, kwasów żółciowych i hormonów sterydowych. Jego utlenione formy zwane oksysterolami są produktem pośrednim w syntezach, ale także regulują metabolizmem cholesterolu poprzez oddziaływanie na receptory komórkowe. Cholesterol jest ważnym składnikiem błon komórkowych. Oksysterole wykazują większą aktywność biologiczną niż sam cholesterol, mając działanie plejotropowe na różne typy komórek organizmu wywołują często przeciwstawne efekty. Oksysterole w przeciwieństwie do cholesterolu mogą przenikać barierę krew-mózg i wpływać na działanie układu nerwowego. Utlenione formy cholesterolu mogą oddziaływać na etiopatogenezę chorób nowotworowych. Podwyższony poziom oksysteroli w tkankach często towarzyszy wielu stanom patologicznym: jak cukrzyca, miażdżyca, demencja lub endometrioza. Utlenione formy cholesterolu mogą hamować lub aktywować różne komórki układu odpornościowego regulując procesami odpowiedzi immunologicznej w przebiegu chorób wirusowych i zapalnych.

show abstract

Cholesterol-25-hydroxylase promotes efferocytosis and resolution of lung inflammation

Cited by 47 publications

References 67 publications

25‐Hydroxycholesterol metabolism is altered by lung inflammation, and its local administration modulates lung inflammation in mice

25‐Hydroxycholesterol metabolism is altered by lung inflammation, and its local administration modulates lung inflammation in mice

Cholesterol metabolism: a new molecular switch to control inflammation

Od glejaka po COVID-19 - rola oksysteroli w organizmie człowieka

Contact Info

Product

Resources

About