<scp>KU</scp>812 basophils express urocortin, <scp>CRH</scp>‐<scp>R</scp>,<scp> MC</scp>1<scp>R</scp> and steroidogenic enzymes and secrete progesterone

Böhm, Markus; Żmijewski, Michał A.; Wasiewicz, Tomasz; Straub, Rainer H.; Raap, Ulrike; Luger, Thomas A.; Slominski, Andrzej

doi:10.1111/j.1600-0625.2012.01513.x

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…This was based on two key observations: (i) that TSPO contained a cholesterol‐binding domain; and (ii) that TSPO density was high in steroid synthesizing cells such as Leydig cells 45,46 . The hypothesis that immune cell surface expression of TSPO is involved in steroidogenesis in these cells would be highly unlikely as immune cells produce little to no steroid proteins 47 . The potential role of TSPO in cholesterol transport, however, could have biologic implications for immune cells with TSPO on their plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

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Surface translocator protein 18 kDa (TSPO) localization on immune cells upon stimulation with LPS and in ART-treated HIV+ subjects

Blevins

Crawford

Azzam

et al. 2020

Journal of Leukocyte Biology

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Translocator protein 18 kDa (TSPO) is a well‐known outer mitochondrial membrane protein and it is widely used as a biomarker of neuroinflammation and brain injury. Although it is thought that TSPO plays key roles in a multitude of host cell functions, including steroid biosynthesis, apoptosis, generation of reactive oxygen species, and proliferation, some of these functions have recently been questioned. Here, we report the unexpected finding that circulating immune cells differentially express basal levels of TSPO on their cell surface, with a high percentage of monocytes and neutrophils expressing cell surface TSPO. In vitro stimulation of monocytes with LPS significantly increases the frequency of cells with surface TSPO expression in the absence of altered gene expression. Importantly, the LPS increase in TSPO cell surface expression in monocytes appears to be selective for LPS because two other distinct monocyte activators failed to increase the frequency of cells with surface TSPO. Finally, when we quantified immune cell TSPO surface expression in antiretroviral therapy‐treated HIV+ donors, a chronic inflammatory disease, we found significant increases in the frequency of TSPO surface localization, which could be pharmacologically suppressed with ∆9‐tetrahydrocannabinol. These findings suggest that cell surface TSPO in circulating leukocytes could serve as a peripheral blood‐based biomarker of inflammation.

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Section: Discussionmentioning

confidence: 99%

“…45,46 The hypothesis that immune cell surface expression of TSPO is involved in steroidogenesis in these cells would be highly unlikely as immune cells produce little to no steroid proteins. 47 The potential role of TSPO in cholesterol transport, however, could have biologic implications for immune cells with TSPO on their plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Surface translocator protein 18 kDa (TSPO) localization on immune cells upon stimulation with LPS and in ART-treated HIV+ subjects

Blevins

Crawford

Azzam

et al. 2020

Journal of Leukocyte Biology

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“…The human gut and colon cancer cells also express glucocorticosteroidogenic activity with production of cortisol and corticosterone and expression of CYP11A1, CYP17A1 and CYP11B1 [49–51]. Other organs which display local steroidogenic pathways in humans are the heart, skin and cells of the immune system (see Table 2) including human basophils [52]. Table 3 shows the expression of steroidogenic genes in different cancers, illustrating their likely capacity to synthesize and/or metabolize steroid hormones as has already been shown with melanoma cells [53, 54].…”

Section: Steroidogenesis In the Skinmentioning

confidence: 99%

Steroidogenesis in the skin: Implications for local immune functions

Slominski

Zbytek

Nikolakis

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

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The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases.

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“…We recently showed that CD300a is upregulated in basophils in mixed leucocyte cultures , and our current aims were to assess its effects on mediator release and signalling using purified basophils. As basophils contribute to the pathophysiology of several skin diseases, particularly allergies , as well as potentially regulating key immunological and even neuroendocrine functions , there is a pressing need to investigate inhibitory mechanisms that can used as therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Expressions and inhibitory functions of CD300a receptors on purified human basophils

Gibbs

Sabato

Bridts

et al. 2012

Experimental Dermatology

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The inhibitory myeloid immunoglobulin receptor CD300a (IRp60) has been shown to downregulate mast cell and eosinophil activities, thereby serving as a potential target for inhibiting allergic effector cell input in allergy. Our aims were to study the expression and functional properties of this receptor in purified human basophils, cells that crucially contribute to Th2-type immunity and allergy. Basophils homogeneously expressed CD300a as well as the inhibitory receptor CD200R on their cell surface, and these expressions increased after anti-IgE stimulation. IgE-mediated basophil degranulation was also significantly inhibited by crosslinking of either CD200R or CD300a (by 90% and 50%, respectively). Inhibitory SHIP-1 phosphorylations were also induced by CD200R and CD300a, although they were not noticeably increased by IgE-dependent activation. We conclude that both CD200R and CD300a play a role in reducing IgE-mediated basophil function and may crucially govern the known differential activities of these cells in vivo.

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KU812 basophils express urocortin, CRH‐R, MC1R and steroidogenic enzymes and secrete progesterone

Cited by 7 publications

References 29 publications

Surface translocator protein 18 kDa (TSPO) localization on immune cells upon stimulation with LPS and in ART-treated HIV+ subjects

Surface translocator protein 18 kDa (TSPO) localization on immune cells upon stimulation with LPS and in ART-treated HIV+ subjects

Steroidogenesis in the skin: Implications for local immune functions

Expressions and inhibitory functions of CD300a receptors on purified human basophils

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