Hello, I’m Raeyoung Kim.
I’m phD student at Neural engineering laboratory in the department of bio and brain engineering.
Today, I am going to introduce you about cytokines and interferon family.
These are my contents.
First, I will explain about general properties of cytokines, cytokine receptors and biopharmaceutical
applications of cytokines.
Then, I will explain about interferons, one of the most famous cytokines family.
Detailed interferon signal transduction pathways will be also explained.
JAK-STAT pathway is one of the examples of interferon signal transduction pathway.
Lastly, the biological effects of interferons will be introduced.
Cytokines are a diverse group of regulatory proteins or glycoproteins.
Various molecules are considered as cytokines but the classification of cytokines are still
remains somewhat diffuse.
Recently, cytokines are grouped as six families based on the structural characteristics.
The detailed names of cytokines are indicated in the table.
Most cytokines have similar functions.
These are the general properties of cytokines.
Cytokines are very potent regulatory molecules.
Nanomolar to picomolar concentrations can be effective.
Cytokines are produced by various cell types and each cell type can produce more than one
cytokines.
They are also pleiotropic, which means they can affect a variety of cell types.
The effect can be same or different depends on the cell types.
Cytokines can usually induce the target cells to secrete other cytokines.
A number of cytokines can induce similar biological effect and it is called redundancy of cytokines.
Cytokine receptors are composed of two parts.
One is ligand interaction part.
This part has unique structure to each cytokines.
Another part is signal transduction initiation part.
This part is often shared by various receptors.
For signal transduction initiation, additional elements are sometimes involved.
The figure is the example of cytokine receptors.
IL-6, IL-11 and LIF receptors, are all composed of a ligand-specific binding domain and a
separate subunit which is called gp130.
gp 130 initiates signal transduction and it is identical in all three receptors.
Cytokines are utilized in the field of biopharmaceuticals.
It coordinate the immune and inflammatory responses in human body.
For instance, EPO stimulates red blood cell production and growth factors are involved
in wound healing.
Neurotropic factors reduces certain neurodegenerative disease.
Cytokines are also related to immunological responses and viral attacks and sometimes
interrupt normal cytokine-based immunological responses.
On the other hand, ytokines overproduction causes a variety of medical conditions.
Pro-inflammatory cytokines such as IL-6 or TNF are implicated in the pathogenesis like
septic shock and rheumatoid arthritis.
Inhibiting such cytokines may provide an effective therapeutic method.
From now on, I will explain about the interferons.
They are the first family of cytokines to be discovered.
Researchers found that some animal cells secretes certain substances when they are exposed to
viral attack.
This substances are started to be called as interferons.
Most species produce a variety of interferon including human.
Humans produce three classes of interferon, IFN-α, IFN-β and IFN-γ.
Based on the structural difference, these interferon are divided as two groups, type
I and II.
IFN-α and IFN-β share the same receptor and IFN-γ binds to a separate receptor and
incudes a different range of biological activities.
Interferons are mostly involved in immune responses.
They induce cellular resistance to external viral attacks.
They regulate immune function and growth and differentiation of cell types.
Sometimes, they regulate the sustenance of early phases of pregnancy of certain animal
species.
Like other cytokines, interferons are also have signal transduction pathway.
Interferons are bind to its receptors on cell surface and initiates signal transduction.
The induced products are regulatory factors of gene expression.
They binds to ISRE, interferon-stimulated response element.
ISRE stimulates RNA polymerase II-mediated transcription.
The induced gene products mediate antiviral and immunomodulatory effects.
JAK-STAT pathway plays a dominant role in mediating signal transduction for many cytokines.
Janus kinases are a family of protein tyrosine kinase.
They have two active sites which is the origin of their name.
They associate with the intracellular domain of many cytokine receptors and remain catalytically
inactive until cytokines bind to the receptor.
STAT is a family of cytoplasmic proteins and function as signal transducers and activators
of transcription like its name.
JAK-STAT pathways have considerable crosstalk between various JAK- and STAT-dependent signaling
pathways.
The signal transduction of JAK-STAT pathway is as in the following.
Cytokines bind to receptor and initiates receptor dimerization.
Associated JAKs are brought closely to the receptors and phosphorylation occurs.
JAKs transphosphorylate each other and tyrosine residues are also phosphorylated.
STATs are activated by JAKs, by phosphorylation and are translocated into the nucleus.
They directly regulate the expression level of interferon and other cytokine-sensitive
genes.
The interferons have several biological effects.
Type I interferons usually function as antiviral and anti-tumour factors.
Type II interferons have various functions.
They potentiates type I IFN activities.
They regulate immune and inflammatory responses.
They also involved in macrophage activation.
The interferons mostly promotes antiviral activity.
Interferon JAK-STAT pathways produce antiviral gene products.
They are usually enzymes such as 2’-5’ oligoadenylate synthetase and eIF-2α protein
kinase.
I will explain details of those two enzymes from now on.
2’-5’ oligoadenylate synthetase synthesize 2’-5’ oligoadenylate.
It has different structure with normal oligoadenylate.
The phosphodiester linkage is formed between 2st and 5th carbon in contrast to usual 3’-5’
linkage.
The 2’-5’ oligoadenylate synthetase system mainly works as an antiviral pathway.
When an interferon binds to a receptor, 2’-5’ oligoadenylate synthase are synthesized.
The invaded external viruses produce double stranded RNA and this activates 2’-5’
oligoadenylate synthase.
As a result, 2’-5’ oligoadenylate is produces and it activates endo-Rnase.
This RNase cleaves single stranded RNA that viral RNA is degraded. 2’-5’ phosphodiesterase
works has an off switch of this pathway by rapidly degrades 2’-5’ oligoadenylate.
The eIF-2α protein kinase also function as an antiviral system.
Interferon binding causes eIF-2α protein kinase synthesis.
Viral-derived double stranded RNA activates eIF-2α protein kinase.
The activated kinase phosphorylate eIF-2α protein and it blocks construction of ribosomal
subunit.
Therefore, the viral mRNA translation is blocked.
The eIF-2α protein kinase is induced by type I IFN in human.
This is the end of my presentation.
Thank you for listening.