Title:Heat Shock Proteins: Therapeutic Perspectives in Inflammatory Disorders
Volume: 10
Issue: 2
Author(s): Rekha Khandia*, Ashok K. Munjal*, Hafiz M. N. Iqbal*Kuldeep Dhama*
Affiliation:
- Department of Biochemistry and Genetics, Barkatullah University, Bhopal-462 026, Madhya Pradesh,India
- Department of Biochemistry and Genetics, Barkatullah University, Bhopal-462 026, Madhya Pradesh,India
- ENCIT - Science, Engineering and Technology School, Tecnologico de Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey, N.L., CP 64849,Mexico
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly- 243 122, Uttar Pradesh,India
Keywords:
Heat shock proteins (HSPs), inflammation, IL-10, molecular chaperon, necroptosis, NF-κB pathway, Tregs, TLR.
Abstract: Background: Heat shock proteins (HSPs) are highly conserved proteins
present in all kingdoms of organisms. These are expressed under stress conditions in
order to protect the cells from injuries. The stress induced protein denaturation is rectified
by refolding and remodelling. These are intracellular proteins but can be present
in extracellular fluid like serum of the patients suffering from trauma, autoimmune
and inflammatory disorders. Virtually in most inflammatory diseases, immune response
towards HSPs is developed.
Objective: The present review expedites the role of HSPs in inflammatory process and
associated disorders, mainly in context to HSP70 and HSP90.
Method: Commencing a thorough survey of the literature and patents available on
HSPs and their role in the process of inflammation, from the authentic published resources available on
Medline, Pubmed, Pubmed Central, Science Direct and other scientific databases; the information retrieved
has been compiled and analyzed.
Results: HSPs modulate the process of inflammation by producing anti-inflammatory cytokines in
chronic inflammatory disease. HSPs mediated expression of IL10 contributes in anti-inflammatory role
via TLR2 and TLR4-dependent mechanisms. Necroptosis, a caspase independent programmed apoptosis
plays an important role in progression of several inflammatory disorders and its major components
MLKL and RIPK-1 are the clients of HSP. Necroptosis is also involved in exposure of several damageassociated
molecular patterns (DAMPs) including HSPs in extracellular environment leading to inflammation.
Endocytosed or intracellular HSP70, is presented by MHC-II molecules and in absence of proper
co stimulation, it lead to expansion of tolerogenic or regulatory T cells (Tregs) responses, which have
inflammation suppressive activity by virtue of production of anti-inflammatory cytokines, suppression or
killing of effector T cells or bringing the APC into tolerogenic state. HSP induced Tregs play an important
role in combating autoimmunity and inflammation.
Conclusion: Present review gives an insight towards the cause of inflammation and an account of different
HSPs contributing various inflammatory disorders viz. inflammatory bowel disease (IBD), intestinal
inflammation, atherosclerosis, rheumatoid arthritis (RA), multiple sclerosis etc. The importance of HSPs
in handling inflammatory disorders has been depicted in recent patents also.
