The effects of stress on splenic immune function are mediated by the splenic nerve

Wan, Weihua; Vriend, Catherine Y.; Wetmore, Lisa; Gartner, John G.; Greenberg, Arnold H.; Nance, Dwight M.

doi:10.1016/0361-9230(93)90044-c

Cited by 59 publications

(4 citation statements)

References 24 publications

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“…Previous results from our group have demonstrated that peripheral administration of this dose, from this particular batch of LPS is insufficient to cause elevations in CRH mRNA within the PVN, thus suggesting that its actions are mediated via central mechanisms in this study [21]. We have further noted a significant increase in both c-fos mRNA and Fos protein in the PVN and the A1 and A2 regions of the brainstem, confirming previous results concerning activation of the HPA axis and c-fos mRNA and Fos peptide following central injection of immune modulators [11, 29, 30]. We have now extended these observations to examine the role of glucocorticoid hormones in modulating these effects.…”

Section: Discussionsupporting

confidence: 79%

“…In intact animals, following acute stress, there is a peak in c-fos mRNA and plasma CORT concentration after 30 min. This is in contrast to the response to LPS which has a later onset and is more sustained, with peaks in CORT and c-fos expression occuring around 3 h after injection [21, 29, 30, 31]. In a previous study we were unable to determine the presence of c-fos mRNA within the PVN 30 min after LPS, but this increase was apparent after 3 h [21].…”

Section: Discussionmentioning

confidence: 68%

“…However, i.c.v. LPS produces Fos-like immunoreactivity, albeit in fewer neurons within the NTS than following peripheral administration [29, 30, 52]. Similarly, c-fos mRNA expression patterns differ depending on the route of administration of LPS or IL-1β [51].…”

Section: Discussionmentioning

confidence: 99%

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Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

et al. 1999

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The A1 and A2 brainstem noradrenergic cell groups project to the hypothalamic paraventricular nucleus (PVN), which is involved in integrating the stress response. Bi-directional communication between the brain and immune system is well established, with both neuroendocrine and immune responses being activated by lipopolysaccharide (LPS). The mechanisms underlying such activation and differences between alternative routes of administration remain unclear. We examined activation of the PVN and A1/A2 cell groups, by assessing c-fos mRNA, or counting Fos-positive neurons in either the PVN or in brainstem A1/A2 cell groups 3 h after intracerebroventricular (i.c.v.) LPS, in control and adrenalectomized (ADX) rats. We also measured corticotropin-releasing hormone (CRH) mRNA in the PVN, and plasma corticosterone (CORT) levels. A group of ADX/CORT-replaced animals received i.c.v. LPS, and CRH mRNA and Fos peptide in the PVN were analysed. ADX increased CRH mRNA in the PVN, as did LPS, but no enhancement of this response was seen in LPS/ADX animals. C-fos mRNA also increased in both the PVN and the A2 cell group following LPS, but this response was potentiated by ADX. Fos peptide-containing cells increased in the PVN and A2 following LPS, and this change was amplified by ADX. Only 11.25% of Fos was found in DBH-positive (putative noradrenergic) neurons, suggesting activation of neurons containing other transmitters. ADX/LPS/CORT animals showed numbers of Fos neurons in the brainstem, and CRH mRNA levels in the PVN which were comparable to intact/LPS animals. Central LPS activates the hypothalamo-pituitary-adrenal axis, a process mediated partly by brainstem noradrenergic neurons, suggesting the involvement of afferent/efferent pathways within the brain. Peripheral administration of LPS involves activation of vagal inputs leading to the nucleus tractus solitarius. We suggest that centrally administered LPS activates the A2 cell group by a mechanism independent of the vagus. In the absence of CORT, despite the lack of a CRH mRNA response, an exaggerated c-fos and peptide response to LPS is observed, which is reversed following CORT pretreatment.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 68%

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Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

et al. 1999

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“…Regarding the skin tissue, it is known that exposure is daily and generally chronic, which has motivated several studies to evaluate its effects using human skin cells as in vitro models. 12–16 However, it is worth mentioning that there is still an enormous difficulty in understanding its real toxic effects, due to the nanoparticles diversity as well as the scientific protocols used, which makes it difficult to compare the results obtained and the reasonability of its safety to human health.…”

Section: Introductionmentioning

confidence: 99%

Functionalized Titanium Nanoparticles Induce Oxidative Stress and Cell Death in Human Skin Cells

Brassolatti¹,

Rodolpho²,

Godoy³

et al. 2022

IJN

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Purpose Nanoparticles are resources of advanced nanotechnology being present in several products. Titanium dioxide nanoparticles are among the five most widely used NP currently expanding their benefits from the oil industry to the areas of diagnostic medicine due to their properties and small size. However, its impact on human health is still controversial in the literature. We aimed to evaluate the cytotoxicity of a new titanium NP functionalized with sodium carboxylic ligand (COOH − Na + ) in human keratinocytes (HaCaT) and human fibroblasts (HDFn). Methods The physical-chemical characterization was performed by the transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential techniques, respectively. MTT and LDH assays were used to assess cytotoxicity and cell membrane damage respectively, ELISA to identify the inflammatory profile and, reactive oxygen species assay and cytometry to detect reactive oxygen species and their relationship with apoptosis/necrosis mechanisms. Results The results demonstrated a decrease in cell viability at the highest concentrations tested for both cell lines, but no change in LDH release was detected for the HaCaT. The cell membrane damage was found only at 100.0 µg/mL for the HDFn. It was demonstrated that cytotoxicity in the highest concentrations evaluated for both cell lines for the 72 h period. The HDFn showed damage to the cell membrane at a concentration of 100 µg/mL followed by a significant increase in reactive oxygen species production. No inflammatory profile was detected. The HaCaT showed apoptosis when exposed to the highest concentration evaluated and HDFn showed both apoptosis and necrosis for the same concentration. Conclusion Thus, it is possible to conclude that the cytotoxicity mechanism differs according to the cell type evaluated, with HDFn being the most sensitive line in this case, and this mechanism can be defined in a dose and time dependent manner, since the highest concentrations also triggered death cell.

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Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing

Cano

Sved

Rinaman

et al. 2001

J of Comparative Neurology

205

124

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Splenic immune function is modulated by sympathetic innervation, which in turn is controlled by inputs from supraspinal regions. In the present study, the characterization of central circuits involved in the control of splenic function was accomplished by injecting pseudorabies virus (PRV), a retrograde transynaptic tracer, into the spleen and conducting a temporal analysis of the progression of the infection from 60 hours to 110 hours postinoculation. In addition, central noradrenergic cell groups involved in splenic innervation were characterized by dual immunohistochemical detection of dopamine-beta-hydroxylase and PRV. Infection in the CNS first appeared in the spinal cord. Splenic sympathetic preganglionic neurons, identified in rats injected with Fluoro-Gold i.p. prior to PRV inoculation of the spleen, were located in T(3)-T(12) bilaterally; numerous infected interneurons were also found in the thoracic spinal cord (T(1)-T(13)). Infected neurons in the brain were first observed in the A5 region, ventromedial medulla, rostral ventrolateral medulla, paraventricular hypothalamic nucleus, Barrington's nucleus, and caudal raphe. At intermediate survival times, the number of infected cells increased in previously infected areas, and infected neurons also appeared in lateral hypothalamus, A7 region, locus coeruleus, subcoeruleus region, nucleus of the solitary tract, and C3 cell group. At longer postinoculation intervals, infected neurons were found in additional hypothalamic areas, Edinger-Westphal nucleus, periaqueductal gray, pedunculopontine tegmental nucleus, caudal ventrolateral medulla, and area postrema. These results demonstrate that the sympathetic outflow to the spleen is controlled by a complex multisynaptic pathway that involves several brainstem and forebrain nuclei.

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The effects of stress on splenic immune function are mediated by the splenic nerve

Cited by 59 publications

References 24 publications

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

Central LPS-Induced <i>c-fos</i> Expression in the PVN and the A1/A2 Brainstem Noradrenergic Cell Groups Is Altered by Adrenalectomy

Functionalized Titanium Nanoparticles Induce Oxidative Stress and Cell Death in Human Skin Cells

Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing

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