Cytokines and autoimmune thyroid disease research
Abstract cytokines (Cytokines) role of the thyroid cells in thyroid-stimulating hormone (TSH) together, the thyroid cells induced by major histocompatibility complex (MHC) - ? antigen
abnormal expression, into antigen-presenting cells, leading to
auto-immune pathological damage, the formation of autoimmune thyroid disease (AITD).
Key words cytokines; thyroid cells; thyroid disease
Cytokines by immune cells or immune cells synthesized and
secreted after activation with the regulation and mediated immune response, inflammation of the a group of small molecular weight polypeptides or glycoproteins . From the hematopoietic system, immune system or inflammatory response in activated cells, its cells monocytes, macrophages, lymphocytes, fibroblasts, keratinocytes, endothelial cells, stellate cells, bone marrow cells and glomerular membrane cells were secreting cytokines. Include interleukin (IL), tumor necrosis factor (TNF), interferon (IFN) and so on. These factors participate in an important component of the immune system, through its endocrine, autocrine and paracrine way, regulating thyroid cell differentiation, growth and secretory function, and to participate in autoimmune thyroid disease
(AITD) in the occurrence and development process. This article on Cytokines and AITD nearly 10 years of research are reviewed.
1 cytokine secretion of thyroid function
In immunology, cytokines can be divided into four
categories: (1) has antiviral activity of cytokines, mainly IFN; (2) has immunomodulatory activity of cytokines, with IL-
2, IL-4, IL -5, IL-7, IL-9, IL-10, IL-12, transforming growth
factor (TGF-β); (3) with the inflammatory cytokine-mediated
activity, including TNF, IL-1, IL - 6, etc.; (4) has the
activity of cells of hematopoietic growth factors, including IL-3, colony-stimulating factor (CSF), erythropoietin (EPO) .
Thyroid cells can produce IL-6, TNF-α, IL-1, IFN-r and
other major cytokines.
1.1 Interleukin-6IL-6 is a multifunctional cytokine, may be mediated by immune and inflammatory response. Was using in situ hybridization or RT-PCR techniques, from the molecular
level to prove, thyroid tissues and cells containing IL-6mRNA
[3,4]. In addition, in cultured human and FRTL-5 thyroid cell
line, etc. are still to express IL-6 protein molecules [3,5].
Moreover, thyroid disease devastating the level of serum IL-6
significantly increased . Description of thyroid cells have the ability to produce IL-6. IL-6 may also be monocyte -
macrophages, activated T cells, vascular endothelial cells and fibroblasts, bone marrow stromal cells and other cell secretion. Thyroid cells to produce IL-6 regulation by many
factors, including IL-1 and thyroid-stimulating hormone (TSH)
The role of the most obvious, they can co-stimulate IL-6
synthesis and secretion. IL-1 can also promote the IL-6m RNA
expression. Available data show that tumor necrosis factor (TNF)-α, γ-interferon (IFN-γ), fetal serum, growth factor
and prostaglandin e 2 and so on can also increase the thyroid cells to produce IL-6 .
1.2 tumor necrosis factor-TNF, there are two molecular
forms, namely, TNF-α, TNF-β. TNF apart from thyroid may also be activated extracellular single-core - macrophages, which
can cause hemorrhagic necrosis of tumor tissue, also known as Cachectin. TNF-α can induce a variety of cytokines (IL-1, IL-
6, IL-8, TNF-γ) gene transcription and expression, etc., so that synthesis and release. TNF-β produced by activated
lymphocytes. A combination of both in the same membrane receptor, and has very similar biological functions. TNF has immunomodulatory role in promoting IL-2R and the major
histocompatibility complex class I antigen (MHC-I) expression.
But also the role of TNF and TNFR neutral sphingomyelinase,
hydrolysis of sphingomyelin (SM), generating ceramide (CH), CH, as the first two messenger-activated protein kinase
(CAPK), mediated by apoptosis. In addition, some scholars believe that TNF-dependent conversion of arachidonic acid
(prostaglandins) process to produce free radicals and peroxides, as the first two messengers into the nucleus, resulting in damage to cell DNA chain, and lipid peroxidation, dissolved enzyme enzyme activation and membrane permeability-
increasing protein overflow, resulting in cell lysis .
1.3 IFN-γ, inter alia thyroid cells, IFN-γ by T cells,
macrophages and NK cells to produce, by its very nature as a glycoprotein. IFN has anti-virus, anti-tumor, immunomodulatory
and other biological functions. IFN immune regulation include: the promotion of macrophage phagocytosis, activated NK (natural killer cells) to increase their antigen expression, enhanced target cells sensitized lymphocyte cytotoxicity.
Thyroid cells produced IL-1, IL-6, TNF-α, IFN-γ of
these hormone-like substances, which on the one hand to
maintain the body's steady-state, and are also involved in a
variety of the pathogenesis of autoimmune diseases, thyroid gland micro-environmental damage, thyroid dysfunction .
2 cytokines on the thyroid function
Cytokines are an important class of biological regulators of thyroid, in thyroid function in regulating growth and differentiation play a pivotal role. Them by influencing the antigen-presenting, information transmission, and gene transcription, LgE synthesis and inactivation, the expression of adhesion molecules, multi-faceted regulating immune injury
in thyroid tissue (positive regulatory role), while others suppress the immune injury in thyroid tissue ( negative regulatory role).
The primary function of thyroid cells, synthesis of
thyroglobulin, peroxidase and thyroid hormone secretion. IL-1,
IL-6, IFN-γ, TNF-α and so can reversibly inhibit thyroid cell synthesis of thyroid globulin (Ig), peroxidase (TPO), reduction of three thyroid hormone triiodothyronine (T3) and
four-triiodothyronine (T4) release. Weetman, etc. (1994) Hamilfom et al (1991) to explore the molecular effects of cytokines on thyroid function, suggesting that IL-1, IL-6,
IFN-γ, TNF-α and so can inhibit thyroid globulin and
peroxidase mRNA expression. Kraiem (1990) data indicate that IL-1, IL-6, IFN-γ, TNF-α and so can inhibit thyroid-
stimulating hormone (TSH) stimulation of thyroid cells. Yanmazakj (1996) also mentioned that IL-1, TNF-α can inhibit
thyroid-stimulating hormone-releasing hormone (TRH) release,
IL-1 on thyroid cells, inhibit iodide uptake.
Cytokines on thyroid cells, major histocompatibility complex (MHC) antigen effect. Major histocompatibility complex - ? class I molecules and the body's immune system is closely related to, directly involved in antigen processing and presenting. Normal thyroid cells do not express MHC-?
antigen, but in a variety of cytokines alone or combined effects of impact of thyroid cell MHC-I, MHC-? antigen
expression. Patwardhan (1991) by means of immunofluorescence
and molecular hybridization to prove that cultured thyroid cells stimulated by IFN-γ, not only MHC-I antigen expression
was significantly increased, and the abnormal expression of MHC-? antigen and intercellular adhesion molecule -1 (CAM-1).
IFN-γ alone could stimulate thyroid cells expressed MHC-?
class I antigen. TNF-α and IL-1 alone without expression of
MHC-? antigen, but they can be together to complete expression of the role of IFN-γ. Fang Zheng et al  To
study the TM-TNF-α (transmembrane TNF-α) the relationship
between molecular structure and function, to clarify its target cell apoptosis induced by molecular mechanisms; experiment will be replaced into a 87 amino acid phenylalanine after the , TM-TNF-α on target cell killing was no obvious
change, but its target cell death induced Changes in the way that the target cell death induced by apoptotic changes in a way similar to the S-TNF-α (secreted TNF-α ) Major-mediated
necrosis. Thus it was that the 87 amino acid residues, respectively, with the two receptors can form hydrogen bonds, they can be directly involved in S-TNF-α and receptor binding
[10,11]. TNF-α, IL-1, IL-8 (TNF-α through nuclear factor-KB
increased IL-8 gene expression) can be reduced monocyte expression of MHC-? class I molecules . Thyroid cells
expressed MHC-? type antigens, into antigen-presenting cells
directly involved in the process of immune injury, affecting the immune disorder of thyroid cell function increased.
Wang and other study found that, using IFN-γ and TNF-α
treated mice subjected to thyroid lymphocyte infiltration, the
thyroid gland after 6 weeks at the beginning of the immune destruction of follicular structure of proteins, and thyroid epithelial cell apoptosis. Studies have shown that in
experimental autoimmune thyroiditis, the thyroid follicular cells subjected to the destruction of inflammatory cytokines, which in human Hashimoto's thyroiditis (HT) in the observed similar results. Reposted elsewhere in the paper for free download http://
3-cell factor and thyroid disease
Many clinical data and animal experiments indicate that cytokines and the occurrence of autoimmune thyroid diseases are closely related to . Pathological damage in autoimmune diseases, is actually an inflammatory reaction, Kotani, etc. through the 17 cases of HT in patients with fine-needle
aspiration biopsy of thyroid cells, DNA fragments were observed, and the performance of electron microscopy, and compared with normal thyroid tissue: found in lymphocytes in
patients with HT infiltration of the thyroid cells, DNA fragments at a high positive rate, electron microscopy of apoptotic bodies can be seen that the thyroid-related
apoptosis and lymphocyte infiltration, presumably infiltrating lymphocytes may be the release of some cytokines such as TNF-
α, IFN - γ and so on. Because IL, IFN, TNF, etc. A group of cytokines that regulate the inflammatory cells and thyroid cells, inflammatory cells between the response and infiltration of lymphocytes and thyroid cells, can produce
high levels of cytokines IFN-γ, TNF - α, IL-1, IL-6 and IL-8
and so on, thus increasing the intensity of their role. Some scholars have found that high concentrations of (105U / L) of IL-1, IL-6, TNF-α and IFN-γ can inhibit thyroid-stimulating
hormone (TSH) stimulation of the FRTL-5 cells, sodium / iodide
symporter gene expression and iodine intake [14,15]. Role in a variety of cytokines, as well as other factors such as thyroid-stimulating hormone (TSH) together, thyroid cells induced by major histocompatibility complex - ? antigen
exception developed and translated into presenting cells such as B cells, macrophages cells, dendritic cells, activated T-
lymphocytes, thyroid epithelial cells, and so on, a direct result of autoimmune damage, resulting in severe "auto-injury"
, while thyroid dysfunction, it also further aggravate the immune response, the formation of autoimmune thyroid disease .
Role of cytokines mechanism of target cells is currently believed that cytokine binding to its receptor itself or
receptor cells by receptor-activated, the signal incoming
cells, activated cytoplasmic tyrosine kinase, the protein phosphorylation, gene transcription start achieving The. Signal transduction through the following JAK / STAF (Janus
kinase family and STAT-family) and the Ras / MAPK two ways,
JAK-STAT is through activation of JAK tyrosine kinase phosphorylation of transcription factor STAT. STAT non-
receptor tyrosine kinase pathway, an important transcription factor involved in a variety of cytokine-induced
transcriptional activity, start gene transcription. Such as IL-6, IFN-γ, TNF-α, and IL-8 [18,19]. The Ras / MAPK is
through Ras / MAP kinase phosphorylation and activation of the final result of activation of transcription factors.
In addition, some scholars put forward the role of TNF and TNFR neutral sphingomyelinase hydrolysis of sphingomyelin (Sm), generating neural amide (CH), CH as a second messenger to activate protein kinase C (CAPK), mediated by apoptosis. In the TNF-dependent conversion of arachidonic acid
(prostaglandins) produced in the course of free radicals and peroxides, causing cellular damage to DNA chain, and lipid peroxidation, lysosomal enzyme activation and membrane permeability-increasing protein overflow, resulting in cell
lysis, the formation of autoimmune thyroid disease .
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