variety of compounds that affect Leydig cell function. CXCL10 (cytokine-responsive gene-2) has been shown to be secreted by Leydig cells, macrophages and T cells into the microenvironment of the testis ( Hu et al. 1998 , Goffic et al. 2002 ). CXCL10
Madan L Nagpal, Yue Chen, and Tu Lin
Vincent Ricchiuti, Christine G Lian, Eveline M Oestreicher, Loc Tran, James R Stone, Tham Yao, Ellen W Seely, Gordon H Williams, and Gail K Adler
), the chemokine osteopontin (OPN), and ED-1 (a protein expressed by monocytes/macrophages)). The cardiac levels of PAI-1 protein were increased in rats receiving E 2 when compared with those not receiving E 2 ( Fig. 6 A, P <0.01). Furthermore, E 2
Recent studies have shown that the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), can affect both tissues and cells that are not directly involved in calcium homeostasis. In particular, a role for calcitriol as a regulator of immune cell differentiation and proliferation has been proposed. Specific high-affinity intracellular receptors for calcitriol (VDR) are detectable in activated T cells, and activated macrophages are able to synthesize calcitriol. A possible paracrine mechanism of action has been postulated. Vitamin D may therefore have a similar role to that of other immune regulatory molecules such as cytokines. The precise interaction of calcitriol with the cytokine network is not yet fully defined, but its ability to modulate immune cells in vitro and its association with inflammatory diseases are now well documented. These findings are outlined in this review with particular reference to effects on macrophages and lymphocytes.
Ectopic production of calcitriol
A. P. N. Themmen, R. Molenaar, W. J. Visser, J. F. Jongkind, F. F. G. Rommerts, and H. J. van der Molen
The morphological and steroidogenic properties of preparations of interstitial cells isolated by collagenase treatment from testes of immature and mature rats have been compared.
After additional purification on a Ficoll gradient, 80% of cells from mature rat testes were found to be Leydig cells; 20% were macrophages. Forty to sixty per cent of collagenase-dispersed cells isolated from immature rats were Leydig cells, 37% were mesenchymal cells and there were no macrophages. A preparation in which 90% cells were Leydig cells could be obtained from immature testes after further purification by centrifugation through a Percoll gradient. The distribution of steroidogenic enzymes through the gradient corresponded to the distribution of LH-dependent steroid production. The results indicate that the steroidogenic activity per Leydig cell from mature rats is fourfold greater than the activity in immature rat Leydig cells in control incubations or after stimulation with LH, dibutyryl cyclic AMP or in the presence of 22R-hydroxycholesterol.
J. Endocr. (1987) 112, 361–366
MS Gregory, LA Duffner, DE Faunce, and EJ Kovacs
Previous studies in our laboratory have demonstrated that cell-mediated immune function was suppressed in female, but not male, mice at 10 days after burn injury and was mediated, in part, by increased production of interleukin-6 (IL-6). Because 17beta-estradiol (E(2)) influences immune function after trauma and the hormone is known to regulate IL-6 production, the effect of E(2) on immune function after thermal injury was examined. Increased circulating concentrations of E(2) corresponded with suppressed delayed-type hypersensitivity (DTH) and splenocyte-proliferative responses, and increased circulating concentrations of IL-6 in female mice after burn. Ovariectomy restored the suppressed DTH response and decreased IL-6 concentrations, and administration of exogenous E(2) to both ovariectomized females and intact male mice resulted in a suppressed DTH response. In addition, in vitro treatment with E(2) suppressed splenocyte proliferation in a macrophage-dependent manner and enhanced macrophage production of IL-6. These results strongly suggest that the sex difference in cell-mediated immunity 10 days after burn injury is mediated by altered concentrations of E(2), which in turn modulate key macrophage-derived immunoregulatory cytokines.
Christianne M A Reijnders, Nathalie Bravenboer, Annechien M Tromp, Marinus A Blankenstein, and Paul Lips
) did not express IGF-I mRNA. IGF-I mRNA was expressed in the intracortical endothelial cells of blood vessels (Fig. 4F ) and in the periosteum of control tibiae (data not shown). Some cells of the bone marrow i.e. megakaryocytes, macrophages, and
CP Sewter, JE Digby, F Blows, J Prins, and S O'Rahilly
Tumour necrosis factor-alpha (TNF-alpha), secreted by cells of the macrophage-monocyte lineage, has a well established role in inflammation and host-defence. The more recent discovery that adipocytes also secrete TNF-alpha has led to a substantial body of research implicating this molecule in the insulin resistance of obesity. However, little is known about the normal regulation of TNF-alpha release from human adipose tissue. In particular, it is not known whether adipocyte production of TNF-alpha is responsive to similar or different molecular regulators than those relevant to macrophages. TNF-alpha release from cultured human adipose tissue and isolated adipocytes was examined using an ELISA. Insulin, cortisol or the thiazolidinedione, BRL 49653, did not have a significant effect on TNF-alpha release from adipose tissue or isolated adipocytes. In contrast, lipopolysaccharide (LPS), a major stimulus of TNF-alpha protein production in monocytes and macrophages, resulted in a fivefold stimulation of TNF-alpha release from human adipose tissue. Significant stimulation of TNF-alpha release was also seen from isolated adipocytes, indicating that the increase in TNF-alpha release from adipose tissue in the presence of LPS is unlikely to be entirely attributable to contaminating monocytes or macrophages. Consistent with this observation was the finding that mRNA for CD14, a known cellular receptor for LPS, is expressed in human adipocytes. The increase in TNF-alpha protein release in response to LPS was blocked by an inhibitor of the matrix metalloproteinase responsible for the cleavage of the membrane-bound proform of TNF-alpha, indicating that this release represented regulated secretion and was not due to cell lysis. In conclusion, the regulation of TNF-alpha protein release from human adipose tissue and isolated adipocytes appears to be similar to its regulation in cell types more traditionally implicated in host defence. The production by the adipocyte of a range of molecules involved in host defence-TNF-alpha, factors D, B and C3, interleukin-6, and macrophage colony-stimulating factor--suggest that this cell type may make a significant contribution to innate immunity.
GM Walsh, DW Sexton, and MG Blaylock
Anti-inflammatory therapy in asthma is reliant on corticosteroids, particularly in their inhaled form. However, steroids are rather non-specific in their actions and they also raise concerns regarding compliance and side-effect Issues. Furthermore, a small proportion of patients with asthma fail to respond to oral glucocorticoids even at high doses. This Article will review the role that steroids and membrane receptor ligation play in the induction of eosinophil apoptosis together with the mechanisms by which corticosteroids enhance the disposal of apoptotic eosinophils by both professional and non-professional phagocytes. Eosinophils are thought to be the major pro-inflammatory effector cell in asthma and their persistence in the airways is probably enhanced by the presence of several asthma-relevant cytokines that prolong eosinophil survival by inhibition of apoptosis (interleukin (IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor, IL-9, IL-13, IL-15). In contrast, a number of signals have been described that accelerate apoptosis in human eosinophils including corticosteroids or ligation of membrane receptors (CD95, CD45, CD69). Thus, the load of lung eosinophils in asthmatic disease is likely to be related to a balance in the tIssue microenvironment between pro- and anti-apoptotic signals. Furthermore, removal of apoptotic eosinophils by phagocytosis by alveolar macrophages or bronchial epithelial cells in a specific receptor-mediated way is as important as the process of apoptosis induction. Corticosteroids enhance the recognition and engulfment of apoptotic eosinophils by macrophages or bronchial epithelial cells. Caspases are key intracellular molecules in the control of apoptosis and defects in caspase-induced apoptosis in eosinophils from steroid-resistant individuals may contribute to the molecular mechanisms underlying glucocorticoid insensitivity in these cells. These findings point the way to new and more targeted anti-inflammatory therapy for asthma and may provide important clues for the development of alternative therapies for glucocorticoid resistance.
Charlotte Steenblock, Nicole Bechmann, Felix Beuschlein, Christian Wolfrum, and Stefan R. Bornstein
Obesity is associated with a higher risk of severe COVID-19 and increased mortality. In the current study, we have investigated the expression of ACE2, NRP1, and HMGB1, known to facilitate SARS-CoV-2 cell entry, in adipose tissue from non-COVID-19 control patients with normal weight, overweight and obesity. All factors were expressed, but no significant differences between the groups were observed. Furthermore, diabetes status and medications did not affect the expression of ACE2. Only in obese men, the expression of ACE2 in adipose tissue was higher than in obese women. In adipose tissue from patients that died from COVID-19, SARS-CoV-2 was detected in the adipocytes even though the patients died more than three weeks after the acute infection. This suggests that adipocytes may act as reservoirs for the virus. In COVID-19 patients, the expression of NRP1 was increased in COVID-19 patients with overweight and obesity. Furthermore, we observed an increased infiltration with macrophages in the COVID-19 adipose tissues compared to control adipose tissue. In addition, crown-like structures of dying adipocytes surrounded by macrophages were observed in the adipose tissue from COVID-19 patients. These data suggest that in obese individuals, in addition to an increased mass of adipose tissue that could potentially be infected, increased macrophage infiltration due to direct infection with SARS-CoV-2 and sustained viral shedding, rather than preinfection ACE2 receptor expression, may be responsible for the increased severity and mortality of COVID-19 in patients with obesity.
A. G. Howatson, M. Farquharson, A. Meager, A. M. McNicol, and A. K. Foulis
The distribution of α-interferon in human placental tissue was investigated by immunocytochemical study of paraffin wax-embedded tissue sections using a sheep α-interferon antiserum. Fifty-eight placentas of gestational ages from 8 to 40 weeks were examined.
α-Interferon was present in the syncytiotrophoblast of the chorionic villi of all placentas and was also in macrophages in 28 cases. The appearances suggest production of interferon in human placental trophoblast and, in view of its diverse biological effects, support the concept of a role for α-interferon in the complex series of events required for successful gestation.
J. Endocr. (1988) 119, 531–534