Adipose-derived stem cells decolonize skin Staphylococcus aureus by enhancing phagocytic activity of peripheral blood mononuclear cells in the atopic rats

Staphylococcus aureus (S. aureus ) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S.aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ+/IL-4+ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V+/7-AAD+ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163+ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

Juvenile Obesity Aggravates Disease Severity in a Rat Model of Atopic Dermatitis

PURPOSE: There is increasing epidemiological evidence of an association between childhood obesity and atopic dermatitis, but little is known about the underlying mechanism(s). In the present study, we used a rat model of atopic dermatitis to assess whether juvenile obesity, induced by reduction of litter size, aggravated the signs of atopic dermatitis and, if so, whether this aggravation was associated with changes in plasma concentration of adipokines, such as leptin and adiponectin. METHODS: Dermatitis was induced by neonatal capsaicin treatment. Body weight, dermatitis score, serum IgE, skin nerve growth factor (NGF), serum leptin and adiponectin, and cytokine mRNA expression in the skin lesion were compared between small (SL, 5 pups) and large litters (LL, 15 pups). RESULTS: The body weight of juvenile rats up to 6 weeks of age was significantly heavier in the SL group, compared with those in the LL group. The SL group showed more robust development of dermatitis, and higher levels of serum IgE and skin NGF than the LL group. Additionally, the SL group demonstrated higher levels of leptin and pro-inflammatory cytokine mRNA but lower levels of adiponectin than the LL group. CONCLUSIONS: These results suggest a causal link between a decrease in immunological tolerance, induced by juvenile obesity, and aggravation of atopic dermatitis.

Are Spinal GABAergic Elements Related to the Manifestation of Neuropathic Pain in Rat?

Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists (1 microgram bicuculline/rat and 5 microgram phaclofen/rat), agonists (1 microgram muscimol/rat and 0.5 microgram baclofen/rat) or GABA transporter (GAT) inhibitors (20 microgram NNC-711/rat and 1 microgram SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.

Neuropathic Pain Behaviors and the Change of Spinal Neuropeptides following Peripheral Nerve Injury in Neonatal Rats

OBJECTIVE: It has been suggested that the occurrence of persistent pain signal during the early postnatal period may alter an individual's response to pain later in life. The aim of this study is to assess whether neonatal nerve injury resulted in long-lasting consequences on nociceptive system in the rat. METHODS: We examined whether neuropathic pain behaviors and the changes of spinal neuropeptides (SP, CGRP, VIP and VIP) induced by peripheral nerve injury within 1 day after birth (Neonate group) were different from those at 8 weeks after birth (Mature group). RESULTS: The Neonate group showed more robust and long-lasting pain behaviors than the Mature group. Immunohistochemical findings demonstrated that spinal SP- & CGRP-immunoreactivities(ir) of the ipsilateral to the contralateral side increased in the Neonate group, whereas those decreased in the Mature group. In addition, increase in spinal VIP- & NPY-ir of the ipsilateral to the contralateral side was more robust in the Mature group than in the Neonate group. CONCLUSION: These results suggest that peripheral nerve injury in the early postnatal period may result in long-lasting and potentially detrimental alterations in nociceptive pathways.

Does HSP70 Induced by Amphetamine Prevent Renal Ischemia/Reperfusion Injury in Rat? / 대한신장학회잡지

BACKGROUND: Heat shock proteins (HSPs) induced by variable kinds of stress produce tolerance to a variety of adverse conditions. However, the protective effect of HSP on ischemia/reperfusion injury (I/R injury) of kidney in vivo remains unclear. The present study was designed to evaluate whether HSP70 induced by hyperthermic preconditioning had renoprotective effect on I/R injury of the kidney in vivo. METHODS: 82 Sprague-Dawley male rats were used. Animals in control group (n=24) were subjected to bilateral occlusion of renal pedicles for 30 or 60 minutes followed by 24-hour reperfusion. In amphetamine (Amp, n=18) and quercetin (Q, n=16) group, amphetamine sulfate, a sympathomimetic drug which can elevate the body temperature as a result of enhanced endogenous lipolysis, and quercetin, a biflavonoid which inhibit the expression of HSP, were injected 4 hours prior to renal ischemia, respectively. In quercetin-amphetamine (QAmp, n=7) group, quercetin was injected 1 hour before administration of amphetamine. AA (n=8) or QQ (n=9) group was identical to Amp or Q group except that sham operation was performed instead of ischemic insult. In all groups, animals were sacrificed prior to or 24 hours after I/R injury. HSP70 induction was confirmed by immunohistochemistry. To assess the I/R injury of kidney, BUN, Cr, histopathologic change of tubular cell and HSP70 expression were evaluated. RESULTS: In Amp group, an increase of BUN and Cr were significantly lower than other groups and less severe renal tubular injury was also observed. In addition, HSP70 was strongly expressed in Amp group, whereas HSP70 was weakly expressed in control group and not expressed in QAmp and Q group. There were no differences in the functional and histologic injuries of kidney after I/R injury between AA, QQ and control group. CONCLUSION: These data demonstrate that the renoprotective effect by amphetamine preconditioning to I/R injury is linked with the expression of HSP70.