Toll-like Receptor 1/2 Agonist Pam3CSK4 Suppresses Lipopolysaccharide-driven IgG1 Production while Enhancing IgG2a Production by B Cells

Lee, Sang-Hoon,Park, Seok-Rae 한국조명·전기설비학회 2018 한국조명·전기설비학회 학술대회논문집 Vol. No.

<P>Interaction between pathogen-associated molecular patterns and pattern recognition receptors triggers innate and adaptive immune responses. Several studies have reported that toll-like receptors (TLRs) are involved in B cell proliferation, differentiation, and Ig class switch recombination (CSR). However, roles of TLRs in B cell activation and differentiation are not completely understood. In this study, we investigated the direct effect of stimulation of TLR1/2 agonist Pam3CSK4 on mouse B cell viability, proliferation, activation, Ig production, and Ig CSR <I>in vitro</I>. Treatment with 0.5 µg/ml of Pam3CSK4 only barely induced IgG1 production although it enhanced B cell viability. In addition, high-dosage Pam3CSK4 diminished IgG1 production in a dose-dependent manner, whereas the production of other Igs, cell viability, and proliferation increased. Pam3CSK4 additively increased TLR4 agonist lipopolysaccharide (LPS)-induced mouse B cell growth and activation. However, interestingly, Pam3CSK4 abrogated LPS-induced IgG1 production but enhanced LPS-induced IgG2a production. Further, Pam3CSK4 decreased LPS-induced germline γ1 transcripts (GLTγ1)/GLTε expression but increased GLTγ2a expression. On the other hand, Pam3CSK4 had no effect on LPS-induced plasma cell differentiation. Taken together, these results suggest that TLR1/2 agonist Pam3CSK4 acts as a potent mouse B cell mitogen in combination with TLR4 agonist LPS, but these 2 different TLR agonists play diverse roles in regulating the Ig CSR of each isotype, particularly IgG1/IgE and IgG2a.</P>

Toll-like Receptor 1/2 Agonist Pam3CSK4 Suppresses Lipopolysaccharide-driven IgG1 Production while Enhancing IgG2a Production by B Cells

이상훈,박석래 대한면역학회 2018 Immune Network Vol.18 No.1

Interaction between pathogen-associated molecular patterns and pattern recognition receptors triggers innate and adaptive immune responses. Several studies have reported that toll-like receptors (TLRs) are involved in B cell proliferation, differentiation, and Ig class switch recombination (CSR). However, roles of TLRs in B cell activation and differentiation are not completely understood. In this study, we investigated the direct effect of stimulation of TLR1/2 agonist Pam3CSK4 on mouse B cell viability, proliferation, activation, Ig production, and Ig CSR in vitro. Treatment with 0.5 μg/ml of Pam3CSK4 only barely induced IgG1 production although it enhanced B cell viability. In addition, high-dosage Pam3CSK4 diminished IgG1 production in a dose-dependent manner, whereas the production of other Igs, cell viability, and proliferation increased. Pam3CSK4 additively increased TLR4 agonist lipopolysaccharide (LPS)-induced mouse B cell growth and activation. However, interestingly, Pam3CSK4 abrogated LPS-induced IgG1 production but enhanced LPS-induced IgG2a production. Further, Pam3CSK4 decreased LPS-induced germline γ1 transcripts (GLTγ1)/GLTε expression but increased GLTγ2a expression. On the other hand, Pam3CSK4 had no effect on LPS-induced plasma cell differentiation. Taken together, these results suggest that TLR1/2 agonist Pam3CSK4 acts as a potent mouse B cell mitogen in combination with TLR4 agonist LPS, but these 2 different TLR agonists play diverse roles in regulating the Ig CSR of each isotype, particularly IgG1/IgE and IgG2a.

Oral Administration of Vaccinium uliginosum L. Extract Alleviates DNCB-Induced Atopic Dermatitis in NC/Nga Mice

김강현,정세영 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.12

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that responds to the interplay of environmental, immunological, and genetic factors. To explore the effect of Vaccinium uliginosum (VU) extract on AD, we orally administrated VU total water extract to AD-induced NC/Nga mice. VU extract reduced AD-like skin lesions, ear thickness, and the frequency of scratching episodes in a time-dependent manner. VU also suppressed the levels of IgE and histamine and the ratio of IgG1/IgG2a in the serum of AD-induced NC/Nga mice. VU administration resulted in the reduction of splenic cytokine production, epidermal thickening, and the infiltration of eosinophils, mast cells, and degranulated mast cells induced by 2,4-dinitrochlorobenzene (DNCB). In addition, VU significantly reduced the mRNA expression of chemokine ligands in dorsal skin. Total water extract and subfractions of VU inhibited interleukin (IL)-4 production in splenocytes, suggesting that VU total extract has a Th2 cytokine modulating effect. These results suggest that the VU total water extract could be a candidate therapeutic agent for the treatment of AD through an immunoregulatory effect.

Baicalein, wogonin, and Scutellaria baicalensis ethanol extract alleviate ovalbumin-induced allergic airway inflammation and mast cell-mediated anaphylactic shock by regulation of Th1/Th2 imbalance and histamine release

Thi Tho Bui,Chun Hua Piao,Chang Ho Song,Chang-Hyun Lee,Hee Soon Shin,Ok Hee Chai 대한해부학회 2017 Anatomy & Cell Biology Vol.50 No.2

Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells.

Local immune response to primary infection and re-infection by <i>Clonorchis sinensis</i> in FVB mice

Kim, Eun-Min,Yu, Hak Sun,Jin, Yan,Choi, Min-Ho,Bae, Young Mee,Hong, Sung-Tae Elsevier 2017 Parasitology international Vol.66 No.4

<P><B>Abstract</B></P> <P>Although <I>Clonorchis sinensis</I> lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to <I>C. sinensis</I>, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (<I>P</I> <0.001). Kupffer cells expressed Th2-related cytokines (IL-10 and IL-13) during primary infection. In addition, serum levels of <I>C. sinensis</I>-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of <I>C. sinensis</I>-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with <I>C. sinensis</I>, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Worm recovery rate in reinfection (RI) was 66.8% at 1w and 81.8% at 4w. </LI> <LI> Kupffer cells direct local immune response Th2 dominant in primary infection of <I>C.s.</I> </LI> <LI> Increased B cells are correlated with the protection to reinfection in mice. </LI> <LI> IgG1, IgG2a, and IgE levels are correlated with the protection to reinfection. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Toll-like Receptor 1/2 Agonist Pam3CSK4 Suppresses Lipopolysaccharide-driven IgG1 Production while Enhancing IgG2a Production by B Cells

Sang-Hoon Lee,Seok-Rae Park 대한면역학회 2018 Immune Network Vol.18 No.1

감초가 면역반응에 미치는 영향(I) -50% 메탄올 엑스의 면역조절작용-

한종현(Jong Hyun Han),오찬호(Chan Ho Oh),은재순(Jae Soon Eun) 대한약학회 1991 약학회지 Vol.35 No.3

These experiments were conducted to investigate the effects of Glycyrrhizae Radix extract(GR) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, Ca2+ uptake by macrophage-like P388D1 cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, Ca2+ uptake and plaque forming cell were determined by enzyme isotope method, [3H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5mcCi/ml 45Ca2+ to P388D1 cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GR(10-3g/ml). Histamine production in mouse spleen cell culture was significantly increased by 48 hour incubation added 0.25mcg/ml of Con A. Con A-dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25mcg/ml of Con A. GR depressed histamine contents at 10-9-10-4mcg/ml and Con A (0.25 mcg/ml) dependent T-lymphocyte proliferation at 10-5-10-4g/ml. IL-1 activity was significantly decreased by 10-8-10-4g/ml of GR. Ca2+ uptake was not changed by GR, but antibody production markedly increased at 10.0-50.0mg/kg of GR. From the above results, it is suggested that GR have immuno-regulatory action; GR decreased cell-mediated immune response and increased antibody production by B lymphocyte at high doses.

Effect of Bifidobacteria on Production of Allergy-Related Cytokines from Mouse Spleen Cells

( Hye Young Kim ),( Jin Oh Yang ),( Geun Eog Ji ) 한국미생물생명공학회 2005 Journal of microbiology and biotechnology Vol.15 No.2

淫羊藿 水抽出物이 생쥐의 면역글로불린 및 Cytokine 생성에 미치는 영향

최용덕,이창현,이상룡,육상원,김정훈,우원홍,이광규 대한동의병리학회 2001 동의생리병리학회지 Vol.15 No.2

This present study was carried out to investigate the body weight-regulatory effects of several herbs(Plantaginis Semen; PLS, Zeas Stigma; ZS, Sophorae Radix; SR) in high fat diet-induced obese rats. Control group rats were fed with high fat diet and administered normal saline for 8weeks. Experimental groups rats were fed with high fat diet and administered extract of 3 herbs each other for 8weeks. And observed that, body weight of rats and total cholesterol, triglyceride, free fatty acid, total lipid, phospholipid, high density lipoprotein(HDL)-cholesterol, low density lipoprotein(LDL)-cholesterol in serum of rats, and glucose, insulin of rats. The results were as follows: There were significant decrease of serum total cholesterol level in PLS group and ZS group. There were significant decrease of serum total lipid level in PLS group, ZS group and SR group. There were significant decrease of serum phospholipid level in ZS group. There were significant decrease of serum LDL-cholesterol level in ZS group. There were significant decrease of serum glucose level in PLS group and ZS group. According to above mentioned results, Plantaginis Semen, Zeas Stigma and Sophorae Radix were expected to be applied to the prevention or treatment of obesity and its complications. Key word : Body weight-regulation,Obesity, Plantaginis Semen(車前子), Zeas Stigma(玉米□), Sophorae Radix(苦蔘)