骨髓间充质干细胞成骨分化过程中瞬时性受体电位香草精受体5的表达：

背景：目前,钙离子通道的研究仪限r肾脏、小肠、光滑卯母细胞中瞬时性受体电位香草精受体5所表现出来的电生理特性。目的：观察新掣钙离子通道瞬时性受体电位香草精受体5在大鼠骨髓间充质干细胞来源的成骨细胞中的表达及意义。方法：分离、提取、培养大鼠骨髓问充质干细胞,诱导大鼠骨髓间充质干细胞向成骨细胞分化,用免疫组织化学法检测大鼠骨髓问充质干细胞诱导分化的成骨细胞中瞬时性受体电位香草精受体5的表达。结果与结论：实验成功将体外培养大鼠骨髓间充质干细胞诱导培养为成骨细胞。碱性磷酸酶染色和茜素红染色检测结果显示,诱导分化的成骨细胞中胞浆中可见紫黑色和红色的矿化结节。免疫组织化学染色结果显示,诱导的成竹细胞中瞬时性受体电位香革精受体5呈强阳性表达。结果证实,大鼠骨髓间充质千细胞来源的成骨细胞中存在瞬时性受体电位香草精受体5钙离子通道,此通道可能成为调节成骨细胞增殖和分化的候选通道。     

上皮钙离子通道TRPV6在脑外伤合并骨折大鼠模型骨折部位表达的实验研究

目的研究大鼠股骨干骨折合并脑外伤时骨折部位瞬时性受体电位香草精受体6(TRPV6)的表达情况,探讨其与脑外伤促进骨折愈合的相关性。方法 12周雄性SD大鼠80只,随机分为5组,每组16只。A1组为骨折合并脑外伤1周组,A2组为骨折合并脑外伤2周组,B1组为单纯骨折1周组,B2组为单纯骨折2周组,C组为正常对照组。A组制作脑外伤合并股骨干骨折模型,B组制作单纯股骨干骨折模型。摄X线片后截取骨痂,HE染色及Masson染色观察骨痂生长情况及组织形态,免疫组化染色及RT-PCR检测TRPV6的表达。结果标本的HE染色及Masson染色可见骨折合并脑外伤组骨痂形成及成熟度快于单纯骨折组(P0.05);免疫组化结果可见骨痂中TRPV6呈阳性反应,A2组TRPV6阳性表达的光密度平均值高B2组(P0.05)。RT-PCR显示A、B组均有TRPV6 mRNA表达,A2组表达显著高于B2组(P0.05)。结论脑外伤对骨折愈合有促进作用,其机制可能与脑外伤后骨折部位TRPV6表达水平升高相关。     

影响局部骨代谢的细胞化学微环境

目的：分析近年来深入研究的几种影响局部骨代谢的细胞生长调节因子，通过探讨各种功能性分子间的作用和联系，从功能的角度了解其决定因素和影响因素，试图勾勒出骨细胞生长、存活、发挥功能的局部体液化学微环境。资料来源：应用计算机检索Medline 1980—01／2002—12相关骨代谢调节因子的文献，检索词“Bone metabolism，adjusting factors”，并限定文献语言种类为English。同时计算机检索CBM1980-01／2002-12相关骨代谢调节因子的文献，检索词为“骨代谢，调节因子”，并限定语言种类为中文。资料选择：对资料进行初审，选取骨代谢调节因子的文献，开始查找全文。纳入标准：①骨代谢。②调节因子。排除标准：综述文献、重复研究、Meta分析类文章。资料提炼：共收集到57篇关于骨代谢调节因子的文献，纳入22篇符合标准的文献。资料综合：众多的激素、因子共同调节成骨细胞和破骨细胞的代谢活动，它们之间有着协同、促进、抑制的复杂关系，并形成网络。骨组织合成多种生长因子。在骨质疏松发病机制中起着重要作用。成纤维细胞生长因子有利于骨质的生长。血小板衍生生长因子在骨折修复过程中起重要作用。骨是转化生长因子B最大的组织来源和储存库。骨形态发生蛋白在骨间质细胞向成骨细胞转化过程、成骨细胞分化过程以及骨发育和骨形成中起着不可替代的作用。白细胞介素主要由吞噬细胞合成，为多肽类物质。推测P物质在骨的纵向生长过程中可能起调控作用。各种骨代谢影响因子均存在于骨组织中，因而任何时候骨细胞的微环境中都不是只出现某一种因子，也即骨组织代谢是由多种因子同时参与调节。结论：针对影响骨代谢各种功能性分子间的复杂网络关系，在微观领域进行分子结构功能模式的数字化、信息化的研究是其可行的途径，也是极其必要的。     

影响局部骨代谢的细胞化学微环境

目的:分析近年来深入研究的几种影响局部骨代谢的细胞生长调节因子,通过探讨各种功能性分子间的作用和联系,从功能的角度了解其决定因素和影响因素,试图勾勒出骨细胞生长、存活、发挥功能的局部体液化学微环境。资料来源:应用计算机检索Medline1980-01/2002-12相关骨代谢调节因子的文献,检索词“Bonemetabolism,adjustingfactors”,并限定文献语言种类为English。同时计算机检索CBM1980-01/2002-12相关骨代谢调节因子的文献,检索词为“骨代谢,调节因子”,并限定语言种类为中文。资料选择:对资料进行初审,选取骨代谢调节因子的文献,开始查找全文。纳入标准:①骨代谢。②调节因子。排除标准:综述文献、重复研究、Meta分析类文章。资料提炼:共收集到57篇关于骨代谢调节因子的文献,纳入22篇符合标准的文献。资料综合:众多的激素、因子共同调节成骨细胞和破骨细胞的代谢活动,它们之间有着协同、促进、抑制的复杂关系,并形成网络。骨组织合成多种生长因子,在骨质疏松发病机制中起着重要作用。成纤维细胞生长因子有利于骨质的生长。血小板衍生生长因子在骨折修复过程中起重要作用。骨是转化生长因子β最大的组织来源和储存库。骨形态发生蛋白在骨间质细胞向成骨细胞转化过程、成骨细胞分化过程以及骨发育和骨形成中起着不可替代的作用。白细胞介素主要由吞噬细胞合成,为多肽类物质。推测P物质在骨的纵向生长过程中可能起调控作用。各种骨代谢影响因子均存在于骨组织中,因而任何时候骨细胞的微环境中都不是只出现某一种因子,也即骨组织代谢是由多种因子同时参与调节。结论:针对影响骨代谢各种功能性分子间的复杂网络关系,在微观领域进行分子结构功能模式的数字化、信息化的研究是其可行的途径,也是极其必要的。     

瞬时受体电位香草酸亚型1对心血管活动调节作用的研究进展

瞬时受体电位香草酸亚型1(transient receptor potential vanilloid 1,TRPV1)是一类非选择性阳离子通道,广泛分布于脑、感觉神经、背根神经节、胃肠道、肝脏以及膀胱组织。TRPV1激活对心血管相关疾病有一定保护作用,但具体机制尚不明确。本文就TRPV1对心血管活动的调节作用作一综述。     

骨形成与吸收过程中的代谢生化标记物

目的：介绍近20年来国内外关于反映骨形成与吸收的代谢生化标记物的研究概况,以及对诊断代谢性骨病及分型、预测骨丢失和骨折的危险性、监测药物疗效的意义.资料来源：应用计算机检索Pubmed网站1980年以来相关文章,限定文章语言种类为“English”,检索词为“biochemical markers”,“bone turnover”,“osteoporosis”;应用计算机检索中文医学期刊网1980年以来相关文章,检索词为“骨代谢”,“标志物”.资料选择：对资料进行初审,选取目前常用的反映骨形成及吸收的生化标志物.纳入标准：①为骨基质成分.②由成骨细胞和破骨细胞活动而释放至血和尿中.③有明确的测量方法.④有临床指导意义.资料提炼：共收集到英文相关文献405篇,按上述标准纳入19篇;中文相关文献12篇,纳入2篇.其余文献均被排除.资料综合：21篇文章中10篇为机制方面的研究,3篇为测量方法研究,8篇为临床研究.共收集了10个相关指标,其中4个与骨形成相关,6个与骨吸收有关.结论：骨代谢的生化标志物是由成骨细胞和破骨细胞活动而释放至血和尿中的骨基质成分,可以反映整体骨转换率,对诊断代谢性骨病及分型、预测骨丢失和骨折的危险性、监测药物疗效等均有重要的意义.     

叶酸代谢与出生缺陷的关系研究

出生缺陷是指由于遗传因素和／或环境因素等原因引起的出生时存在的各种结构性发育异常和功能性异常的总称。它逐渐成为全球许多国家和地区围产儿、婴儿残疾和死亡的主要原因,它的发生给家庭乃至社会带来严重影响。常见的严重性缺陷有神经管缺陷（NTD）、Down综合征、先天性心脏病、唇腭裂等。近年来许多研究发现,叶酸在预防出生缺陷中具有重要作用,故对叶酸代谢与出生缺陷关系的研究越来越引起人们的重视。     

骨形成与吸收过程中的代谢生化标记物

目的:介绍近20年来国内外关于反映骨形成与吸收的代谢生化标记物的研究概况,以及对诊断代谢性骨病及分型、预测骨丢失和骨折的危险性、监测药物疗效的意义。资料来源:应用计算机检索Pubm ed网站1980年以来相关文章,限定文章语言种类为“English”,检索词为“biochem ical m arkers”,“boneturnover”,“osteoporosis”;应用计算机检索中文医学期刊网1980年以来相关文章,检索词为“骨代谢”,“标志物”。资料选择:对资料进行初审,选取目前常用的反映骨形成及吸收的生化标志物。纳入标准:①为骨基质成分。②由成骨细胞和破骨细胞活动而释放至血和尿中。③有明确的测量方法。④有临床指导意义。资料提炼:共收集到英文相关文献405篇,按上述标准纳入19篇;中文相关文献12篇,纳入2篇。其余文献均被排除。资料综合:21篇文章中10篇为机制方面的研究,3篇为测量方法研究,8篇为临床研究。共收集了10个相关指标,其中4个与骨形成相关,6个与骨吸收有关。结论:骨代谢的生化标志物是由成骨细胞和破骨细胞活动而释放至血和尿中的骨基质成分,可以反映整体骨转换率,对诊断代谢性骨病及分型、预测骨丢失和骨折的危险性、监测药物疗效等均有重要的意义。     

骨代谢与年龄增长的关系

目的：总结并分析随年龄增长人体骨代谢的特征，探讨随年龄增长骨骼的变化，重点探讨老年人，尤其闭经后妇女骨代谢的特征，为防治骨质疏松症提供科学依据。 资料来源：应用计算机检索Medline 1993-01／2003—12年龄增长与骨代谢文章。检索词为“The bone metabolism，The age growth，”并限定文章语种为English。同时从图书馆人工检索1993—01／2003—12的日文资料中有关年龄增长与骨代谢相关的文章。 资料选择：对资料进行初审，纳入标准：①关于随年龄增长骨骼的生理性变化特征、机制、影响因素。②对临床病例回顾性研究分析；排除重复性研究内容。 资料提练：符合上述要求的文章21篇，排除14篇重复性研究。7篇符合纳入标准：其中3篇为研究性论著，2篇为诊断标准，2篇为教科书。 资料综合：随年龄增长骨代谢变化很大，在生长期骨骼逐渐成熟，骨骼钙量逐渐增加。一般到20岁以后骨代谢处于动态平衡，40岁以后骨代谢呈负增长，骨骼钙量减少。骨代谢变化是随年龄增长最剧烈、变化量最大的一个参数。老年人，尤其是妇女闭经后骨质疏松发生率增长很快，除因老年人退行性变外，还与内分泌紊乱等多种因素相关，通过研究为防治骨质疏松症提供科学依据。 结论：在了解年龄增长与骨代谢关系的基础上，认识到防治骨质疏是可能的，主要是建立健康的生活方式，注意营养全面，摄入足量的含钙高的食物。     

儿童单纯性肥胖与心血管代谢及骨代谢的关系研究

目的 探讨儿童单纯性肥胖与心血管代谢及骨代谢的关系,以期为防治儿童肥胖及相关疾病提供理论支持。方法选择2019年10月至2020年12月诊断为单纯性肥胖的75例儿童作为肥胖组,选择同时期进行健康体检的75例儿童作为对照组。比较两组的基础资料、心血管代谢指标及骨代谢指标,分析肥胖组心血管代谢指标、骨代谢指标与身体质量指数（BMI）的关系。结果 肥胖组的体重、BMI、收缩压（SBP）和舒张压（DBP）高于对照组,差异具有统计学意义（P<0.05）。肥胖组的血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）水平均高于对照组,高密度脂蛋白（HDL）水平低于对照组,舒张末期室间隔厚度（IVST）、舒张末期左室后壁厚度（LVPWT）、左室相对室壁厚度（RWT）、左室质量（LVM）明显大于对照组,差异具有统计学意义（P<0.05）;两组的左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）、左室舒张末期容积（LVEDV）、左室收缩末期容积（LVESV）及左室射血分数（LVEF）比较,差异无统计学意义（P>0.05）。肥胖组的25羟维生素D[25(OH)D]水平...     

Mechanisms involved in potentiation of transient receptor potential vanilloid 1 responses by ethanol

The transient receptor potential vanilloid 1 or TRPV1 is a calcium‐permeable ion channel that is activated by capsaicin, the active component of hot chilli peppers, and is involved in the development of inflammatory and neuropathic hyperalgesias. Ethanol can sensitise TRPV1‐mediated responses, but the pathways contributing to the potentiation of TRPV1 by ethanol have not been clearly defined. Since the μ opioid receptor (MOP) agonist morphine can inhibit TRPV1 responses potentiated by cAMP‐dependent protein kinase A (PKA), and ethanol‐mediated modulation of other ion channels involves activation of PKA, we aimed to assess the contribution of MOP‐sensitive pathways to the potentiation of TRPV1‐mediated capsaicin responses by ethanol. Calcium responses elicited by the TRPV1 agonist capsaicin were potentiated by treatment with ethanol, but morphine was not able to inhibit ethanol‐sensitised capsaicin responses. Indeed, cAMP‐dependent PKA did not appear to contribute to potentiation of TRPV1 responses by ethanol, as the PKA inhibitor Rp‐cAMPS did not inhibit ethanol‐potentiated capsaicin responses. Similarly, treatment with specific PKC and PI3K inhibitors did not affect capsaicin responses in the presence of ethanol. However, treatment with wortmannin at concentrations reported to cause PIP2 depletion limited the ability of ethanol to sensitise TRPV1‐mediated capsaicin responses. Among other plausible mechanisms, such as non‐specific inhibition of kinases including mTOR, DNA‐PK, MLCK, MAPK and polo‐like kinases, this suggests that ethanol may affect the PIP2‐TRPV1 interaction. This was confirmed by inhibition of ethanol‐potentiation by the PLC inhibitor U73122. The results presented here suggest that morphine may be of limited use in inhibiting nociceptive TRPV1 responses that have been sensitised by exposure to ethanol.     

骨代谢与年龄增长的关系

目的:总结并分析随年龄增长人体骨代谢的特征,探讨随年龄增长骨骼的变化,重点探讨老年人,尤其闭经后妇女骨代谢的特征,为防治骨质疏松症提供科学依据。资料来源:应用计算机检索Medline1993-01/2003-12年龄增长与骨代谢文章。检索词为“Thebonemetabolism,Theagegrowth,”并限定文章语种为English。同时从图书馆人工检索1993-01/2003-12的日文资料中有关年龄增长与骨代谢相关的文章。资料选择:对资料进行初审,纳入标准:①关于随年龄增长骨骼的生理性变化特征、机制、影响因素。②对临床病例回顾性研究分析;排除重复性研究内容。资料提练:符合上述要求的文章21篇,排除14篇重复性研究。7篇符合纳入标准:其中3篇为研究性论著,2篇为诊断标准,2篇为教科书。资料综合:随年龄增长骨代谢变化很大,在生长期骨骼逐渐成熟,骨骼钙量逐渐增加。一般到20岁以后骨代谢处于动态平衡,40岁以后骨代谢呈负增长,骨骼钙量减少。骨代谢变化是随年龄增长最剧烈、变化量最大的一个参数。老年人,尤其是妇女闭经后骨质疏松发生率增长很快,除因老年人退行性变外,还与内分泌紊乱等多种因素相关,通过研究为防治骨质疏松症提供科学依据。结论:在了解年龄增长与骨代谢关系的基础上,认识到防治骨质疏是可能的,主要是建立健康的生活方式,注意营养全面,摄入足量的含钙高的食物。     

Effect of paclitaxel on transient receptor potential vanilloid 1 in rat dorsal root ganglion

Peripheral neuropathy is a common adverse effect of paclitaxel treatment. To analyze the contribution of transient receptor potential vanilloid 1 (TRPV1) in the development of paclitaxel-induced thermal hyperalgesia, TRPV1 expression in the rat dorsal root ganglion (DRG) was analyzed after paclitaxel treatment. Behavioral assessment using the tail-flick test showed that intraperitoneal administration of 2 and 4 mg/kg paclitaxel induced thermal hyperalgesia after days 7, 14, and 21. Paclitaxel-induced thermal hyperalgesia after day 14 was significantly inhibited by the TRP antagonist ruthenium red (3 mg/kg, s.c.) and the TRPV1 antagonist capsazepine (30 mg/kg, s.c.). Paclitaxel (2 and 4 mg/kg) treatment increased the expression of TRPV1 mRNA and protein in DRG neurons. Immunohistochemistry showed that paclitaxel (4 mg/kg) treatment increased TRPV1 protein expression in small and medium DRG neurons 14 days after treatment. Antibody double labeling revealed that isolectin B4-positive small DRG neurons co-expressed TRPV1. TRPV1 immunostaining was up-regulated in paw skin day 14 after paclitaxel treatment. Moreover, in situ hybridization histochemistry revealed that most of the TRPV1 mRNA-labeled neurons in the DRG were small or medium in size. These results suggest that paclitaxel treatment increases TRPV1 expression in DRG neurons and may contribute to functional peripheral neuropathic pain.     

Somatostatin modulates the transient receptor potential vanilloid 1 (TRPV1) ion channel

Activation of peripheral somatostatin receptors (SSTRs) inhibits sensitization of nociceptors, thus having a short term or phasic effect [Pain 90 (2001) 233] as well as maintaining a tonic inhibitory control over nociceptors [J Neurosci 21 (2001) 4042]. The present study provides several lines of evidence that an important mechanism underlying SSTR modulation of nociceptors is regulation of the transient receptor potential vanilloid 1 ion channel (TRPV1, formerly the VR1 receptor). Double labeling of L5 dorsal root ganglion cells demonstrates that 60% of SSTR2a-labeled cells are positive for TRPV1. Conversely, 33% of TRPV1-labeled cells are positive for SSTR2a. In vivo behavioral studies demonstrate that intraplantar injection of 20.0 but not 2.0 μM octreotide (OCT, SSTR agonist) significantly reduces capsaicin (CAP, a ligand for TRPV1) -induced flinching and lifting/licking behaviors. This occurs through local activation of SSTRs in the injected hindpaw and is reversed following co-application of the SSTR antagonist cyclo-somatostatin (c-SOM). In vitro studies using a skin-nerve preparation demonstrate that activation of peripheral SSTRs on nociceptors with 20.0 μM OCT significantly reduces CAP-induced activity and can prevent CAP-induced desensitization. Furthermore, blockade of peripheral SSTRs with c-SOM dramatically enhances CAP-induced behaviors and nociceptor activity, demonstrating SSTR-induced tonic inhibitory modulation of TRPV1. Finally, TRPV1 does not appear to be under tonic opioid receptor control since the opioid antagonist naloxone does not change CAP-induced excitation and does not effect OCT-induced inhibition of CAP responses. These data strongly suggest that SSTRs modulate nociceptors through phasic and tonic regulation of peripheral TRPV1 receptors.     

Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner

Hyperalgesia is a cardinal symptom of opioid withdrawal. The transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated ion channel expressed on sensory neurons responding to noxious heat, protons, and chemical stimuli such as capsaicin. TRPV1 can be inhibited via μ-opioid receptor (MOR)-mediated reduced activity of adenylyl cyclases (ACs) and decreased cyclic adenosine monophosphate (cAMP) levels. In contrast, opioid withdrawal following chronic activation of MOR uncovers AC superactivation and subsequent increases in cAMP and protein kinase A (PKA) activity. Here we investigated (1) whether an increase in cAMP during opioid withdrawal increases the activity of TRPV1 and (2) how opioid withdrawal modulates capsaicin-induced nocifensive behavior in rats. We applied whole-cell patch clamp, microfluorimetry, cAMP assays, radioligand binding, site-directed mutagenesis, and behavioral experiments. Opioid withdrawal significantly increased cAMP levels and capsaicin-induced TRPV1 activity in both transfected human embryonic kidney 293 cells and dissociated dorsal root ganglion (DRG) neurons. Inhibition of AC and PKA, as well as mutations of the PKA phosphorylation sites threonine 144 and serine 774, prevented the enhanced TRPV1 activity. Finally, capsaicin-induced nocifensive behavior was increased during opioid withdrawal in vivo. In summary, our results demonstrate an increased activity of TRPV1 in DRG neurons as a new mechanism contributing to opioid withdrawal-induced hyperalgesia.     

Hypoxia-induced sensitization of transient receptor potential vanilloid 1 involves activation of hypoxia-inducible factor-1 alpha and PKC

The capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1), acts as a polymodal detector of pain-producing chemical and physical stimuli in sensory neurons. Hyperglycemia and hypoxia are two main phenomena in diabetes associated with several complications. Although many studies on streptozotocin-induced diabetic rats indicate that early diabetic neuropathy is associated with potentiation of TRPV1 activity in dorsal root ganglion neurons, its underlying mechanism and distinctive roles of hyperglycemia and hypoxia have not been completely clarified. Here, we show that hypoxic and high glucose conditions (overnight exposure) potentiate the TRPV1 activity without affecting TRPV1 expression in both native rat sensory neurons and human embryonic kidney-derived 293 cells expressing rat or human TRPV1. Surprisingly, hypoxia was found to be a more effective determinant than high glucose, and hypoxia-inducible factor-1 alpha (HIF-1α) seemed to be involved. In addition, high glucose enhanced TRPV1 sensitization only when high glucose existed together with hypoxia. The potentiation of TRPV1 was caused by its phosphorylation of the serine residues, and translocation of protein kinase C (PKC)ε was clearly observed in the cells exposed to the hypoxic conditions in both cell types, which was inhibited by 2-methoxyestradiol, a HIF-1α inhibitor. These data suggest that hypoxia is a new sensitization mechanism for TRPV1, which might be relevant to diabetes-related complications, and also for other diseases that are associated with acute hypoxia.     

Involvement of transient receptor potential vanilloid 1 receptors in protease-activated receptor-2-induced joint inflammation and nociception

Protease-activated receptor-2 (PAR-2) is a G-protein-coupled receptor activated through proteolytic cleavage. It is localized on epithelial, endothelial and inflammatory cells, as well as on transient receptor potential vanilloid 1 (TRPV1) receptor-expressing neurones. It plays an important role in inflammatory/nociceptive processes. Since there are few reports concerning PAR-2 function in joints, the effects of intraarticular PAR-2 activation on joint pain and inflammation were studied. Secondary hyperalgesia/allodynia, spontaneous weight distribution, swelling and inflammatory cytokine production were measured and the involvement of TRPV1 ion channels was investigated in rats and mice. Injection of the PAR-2 receptor agonist SLIGRL-NH₂ into the knee decreased touch sensitivity and weight bearing of the ipsilateral hindlimb in both species. Secondary mechanical allodynia/hyperalgesia and impaired weight distribution were significantly reduced by the TRPV1 antagonist SB366791 in rats and by the genetic deletion of this receptor in mice. PAR-2 activation did not cause significant joint swelling, but increased IL-1β concentration which was not influenced by the lack of the TRPV1 channel. For comparison, intraplantar SLIGRL-NH₂ evoked similar primary mechanical hyperalgesia and impaired weight distribution in both WT and TRPV1 deficient mice, but oedema was smaller in the knockouts. The inactive peptide, LRGILS-NH₂, injected into either site did not induce any inflammatory or nociceptive changes. These data provide evidence for a significant role of TRPV1 receptors in secondary mechanical hyperalgesia/allodynia and spontaneous pain induced by PAR-2 receptor activation in the knee joint. Although intraplantar PAR-2 activation-induced oedema is also TRPV1 receptor-mediated, primary mechanical hyperalgesia, impaired weight distribution and IL-1β production are independent of this channel.