• Biomedical Science Letters
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• v.16 no.2
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• pp.123-126
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• 2010

Volatile organic compounds are commonly off gassed from various building materials and can induce sick building syndrome. Volatile organic compounds such as formaldehyde, xylene and toluene are known as toxic agents in immune cells. Human leukocytes, particularly, neutrophils and eosinophils play important roles in the regulation of immune responses. In this study, we investigated the toxic effects of formaldehyde, ortho-xylene (o-xylene), para-xylene (p-xylene) and toluene on the apoptosis of neutrophils and eosinophils isolated from the blood of healthy donors. Formaldehyde increased the constitutive apoptosis of neutrophils and eosinophils. o-xylene, p-xylene and toluene increased the spontaneous apoptosis of eosinophils, but not that of neutrophils. Formaldehyde increased the protein level of IL-8 in neutrophils and eosinophils, and suppressed the MCP-1 expression in neutrophils. The release of IL-6 from neutrophils was diminished by volatile organic compounds used in this study. In conclusion, formaldehyde, xylene and toluene elevate the apoptosis of neutrophils and eosinophils, and regulate the release of cytokine and chemokine in neutrophils and eosinophils. These results indicate that formaldehyde, xylene and toluene have a cytotoxicity in human neutrophils and eosinophils and may damage the modulation of immune responses.

• Parasites, Hosts and Diseases
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• v.48 no.1
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• pp.1-7
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• 2010

Neutrophils play an important role in the human immune system for protection against such microorganisms as a protozoan parasite, Trichomonas vaginalis; however, the precise role of neutrophils in the pathogenesis of trichomoniasis is still unknown. Moreover, it is thought that trichomonal lysates and excretory-secretory products (ESP), as well as live T. vaginalis, could possibly interact with neutrophils in local tissues, including areas of inflammation induced by T. vaginalis in humans. The aim of this study was to investigate the influence of T. vaginalis lysate on the fate of neutrophils. We found that T. vaginalis lysate inhibits apoptosis of human neutrophils as revealed by Giemsa stain. Less altered mitochondrial membrane potential (MMP) and surface CD16 receptor expression also supported the idea that neutrophil apoptosis is delayed after T. vaginalis lysate stimulation. In contrast, ESP stimulated-neutrophils were similar in apoptotic features of untreated neutrophils. Maintained caspase-3 and myeloid cell leukemia-1 (Mcl-1) in neutrophils co-cultured with trichomonad lysate suggest that an intrinsic mitochondrial pathway of apoptosis was involved in T. vaginalis lysate-induced delayed neutrophil apoptosis; this phenomenon may contribute to local inflammation in trichomoniasis.

• Biomedical Science Letters
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• v.17 no.1
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• pp.89-93
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• 2011

Asthma is an inflammatory airway disease and is characterized by the releases of inflammatory mediators including chemokines. They are mainly associated with the recruitment, activation and dysregulation of specific inflammatory cells, especially neutrophils in neutrophilic asthma. CC chemokines bind to CC chemokine receptors (CCRs) in the surface of their target cells. The aims of this study are to examine the CCR expression in neutrophils of bronchoalveolar lavage fluid (BALF) of asthmatic patients and to determine the alternation of migration and apoptosis of neutrophils by the BALF. We demonstrate that CCR3 strongly expresses in BALF neutrophils of asthmatic patients as compared to other CCRs and increases during apoptosis of the BALF neutrophils. The migration of asthmatic blood neutrophils increases in response to asthmatic BALF as compared to BALF of normal volunteer. In addition, asthmatic BALF includes the higher levels of IL-8 protein than normal BALF and it has no effect on apoptosis of asthmatic blood neutrophils. Taken together, our results indicate that CCR3 expression may be associated with unknown function of asthmatic BALF neutrophils and BALF may be involved in the recruitment of neutrophils into the airway, but not in the neutrophils apoptosis.

• Biomedical Science Letters
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• v.22 no.4
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• pp.211-214
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• 2016

House dust mite is an essential allergen in the pathogenesis of allergic diseases. Abnormal regulation of neutrophil apoptosis is an important pathogenic process in allergic diseases. In the present study, we investigated the effects of house dust mites on spontaneous apoptosis of neutrophils and its associated mechanisms. Extract of Dermatophagoides pteronissinus (DP) inhibited neutrophil apoptosis in a time-dependent manner. Cycloheximide (CHX), an inhibitor of translation, increased apoptosis of DP-treated neutrophils as well as control cells. The pro-apoptotic effect of CHX was blocked by DP in neutrophils. In addition, DP increased the phosphorylation of Bad in a time-dependent manner, indicating that it exerted an inhibitory effect on the function of Bad. These results suggest that DP has anti-apoptotic effects of neutrophils and may regulate protein synthesis and activation of Bad. Moreover, these findings may shed light on elucidation of allergy pathogenesis due to house dust mites.

• Biomedical Science Letters
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• v.18 no.3
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• pp.307-309
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• 2012

(S)-(+)-3(3,4-dihydroxy-phenyl)-acrylic acid 2,2-dimethyl-8-oxo3,4-dihydro-2H,8H-pyrano[3,2-g]Chromen-3-yl-ester (Compound 6, C6) is synthesized from (S)-(+)-decursin and attenuates the pathophysiologic progression of asthma in a ovalbumin-induced asthmatic mouse model. In the present study, we examined the effect of C6 on spontaneous apoptosis of eosinophils and neutrophils of normal and asthmatic subjects. C6 increased the apoptosis of asthmatic eosinophils in a dose-dependent manner, but it inhibited neutrophil apoptosis. C6 has no effect on apoptosis of normal eosinophils and neutrophils. LY294002, an inhibitor of PI3K, rottlerin, an inhibitor of $PKC{\delta}$, Ro-31-8425, an inhibitor of classical PKC inhibitor, PD98059, an inhibitor of MEK, and BAY 11-7085, an inhibitor of NF-${\kappa}B$, blocked the inhibitory effect on apoptosis of asthmatic neutrophils due to C6. These results indicate that C6 may be valuable as a therapeutic agent for the treatment of asthma.

• Journal of Life Science
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• v.21 no.1
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• pp.22-30
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• 2011

Apolipoprotein A-I (apoA-I) has anti-inflammatory and anti-oxidative properties. This study was designed to investigate whether apoA-I affects apoptosis and cytokine production of human blood neutrophils in an in vitro culture system. Spontaneous apoptosis of neutrophils was significantly delayed by apoA-I. In addition, high density lipoprotein containing apoA-I also delayed apoptosis of neutrophils. Apoptosis of neutrophils was inhibited by anti-scavenger receptor type B-I antibodies. The amounts of interleukin-8, interferon (IFN)-inducible protein 10 (IP-10), and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) in the supernatants of cultured neutrophils treated with apoA-I were significantly increased. Combined treatment of neutrophils with IFN-$\gamma$ and apoA-I produced higher amounts of IP-10 and TNF-$\alpha$ than did treatment with IFN-$\gamma$ or apoA-I alone. The present study reveals that apoA-I activates neutrophils to produce cytokines and delays spontaneous apoptosis of neutrophils. These findings suggest that apoA-I, although a well-known negative acute-phase protein, has a pro-inflammatory effect in neutrophils.

• Biomedical Science Letters
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• v.21 no.2
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• pp.122-125
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• 2015

House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-$\gamma$), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-$\beta$). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

• Parasites, Hosts and Diseases
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• v.48 no.4
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• pp.285-290
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• 2010

Tyrosine kinases are one of the most important regulators for intracellular signal transduction related to inflammatory responses. However, there are no reports describing the effects of tyrosine kinases on neutrophil apoptosis induced by Entamoeba histolytica, In this study, isolated human neutrophils from peripheral blood were incubated with live trophozoites in the presence or absence of tyrosine kinase inhibitors. Entamoeba-induced receptor shedding of CD16 and PS externalization in neutrophils were inhibited by pre-incubation of neutrophils with the broad-spectrum tyrosine kinase inhibitor genistein or the Src family kinase inhibitor PP2. Entamoeba-induced ROS production was also inhibited by genistein or PP2, Moreover, genistein and PP2 blocked the phosphorylation of ERK and p38 MAPK in neutrophils induced by E. histolytica. These results suggest that Src tyrosine kinases may participate in the signaling event for ROS-dependent activation of MAPKs during neutrophil apoptosis induced by E. histolytica.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.2
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• pp.102-108
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• 2016

Der p 2 is the major allergen of the house dust mite (HDM) associated with the development of allergic diseases. The pathogenic mechanism of the allergy is related to cytokine release of lymphocytes and constitutive apoptosis of neutrophils. In the present study, we examined whether Der p 2 induces cytokine release of lymphocytes, which is involved in regulation of neutrophil apoptosis. In normal and allergic subjects, Der p 2 enhanced the secretion of IL-6, IL-8, MCP-1, and GM-CSF in a time-dependent manner. Although Der p 2 was weakly effective against neutrophil apoptosis, conditioned media collected from normal and allergic lymphocytes after Der p 2 treatment inhibited the apoptosis of normal and allergic neutrophils. Der p 2 showed stronger inhibition of apoptosis of allergic neutrophils cocultured with allergic lymphocytes than normal neutrophils cocultured with normal lymphocytes. These findings improve our understanding of the role of Der p 2 in regulation of lymphocytes and neutrophils and will enable elucidation of allergy pathogenesis.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.230-236
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• 2015

Dermatophagoides pteronissinus (DP) is one of the house dust mites (HDM) associated with allergic diseases. The cysteine protease Der p 1 from DP is a powerful allergen. The pathogenic mechanism of allergy is involved in cytokine secretion of lymphocytes and spontaneous apoptosis of neutrophils. In this study, we investigated whether Der p 1 induces cytokine secretion of lymphocytes and if the release of cytokines is associated with regulation of neutrophil apoptosis. In normal and allergic subjects, Der p 1 increased IL-6, IL-8, MCP-1, and GM-CSF release in a time-dependent course. Supernatants collected from normal and allergic neutrophils after Der p 1 stimulation suppressed the apoptosis of normal and allergic neutrophils, although Der p 1 alone has no effect on neutrophils. Der p 1 suppressed neutrophil apoptosis in coculture of normal neutrophils with normal lymphocytes. Der p 1 more strongly suppressed apoptosis of allergic neutrophils cocultured with allergic lymphocytes than normal neutrophils cocultured with normal lymphocytes. In summary, Der p 1 increases the secretion of cytokines, which has anti-apoptotic effects on neutrophils of normal and allergic subjects. These results will contribute to elucidate the pathogenic mechanism of allergic diseases.