Leukemia Inhibitory Factor (LIF) is a cytokine that belongs to the interleukin-6 family.
LIF can have opposite effects on different cell types, including stimulating or inhibiting cell proliferation, differentiation, and survival. But while LIF can act on a wide range of cell types, many of its effects are not apparent during normal body function and may become apparent during tissue damage or injury.
The most important actions of LIF in the body are the following:
LIF actions in reproduction
The LIF produced by the endometrial glands (and possibly the blastocyst) acts on the endometrial epithelium to make it receptive to blastocyst adhesion and also acts on the endometrial stroma to make it ready for implantation and growth. placenta. LIF also acts on the inner blastocyst cell mass to maintain cell proliferation during formation and on the outer cell mass to induce trophoblast entry into the endometrium. LIF is important for the formation of the maternal placenta and the balanced activity of LIF is essential for the formation of giant trophoblast cells as well as for the proper architecture of the villi layer in which the maternal and fetal blood come into contact.
Actions of LIF in Bone Formation
LIF acts on bone stromal cells enhances their differentiation into bone-forming osteoblasts and inhibits the production of sclerosin (a substance that inhibits osteoblastic activity) by osteocytes. Osteoblasts under the action of LIF produce a cytokine that acts on macrophages to differentiate them into multinucleated osteoclasts that absorb bone. These associated phenomena allow the repair of damaged bone, starting first with the clearance of the damaged bone and then causing the formation of new bone.
LIF actions on the hypothalamic-pituitary-adrenal axis
LIF acts on the anterior pituitary gland to enhance the differentiation of cell precursors into corticotropes and stimulates ACTH secretion by corticotrope cells synergistically with the corticotropin-releasing hormone (CRH) produced by hypothalamic neurons. ACTH acts on the adrenal cortex to secrete cortisol, a substance with many actions.
Neuromuscular effects of LIF
LIF acts on nerve stem cells to increase their self-renewal and may also act to stimulate the production and survival of neurons and has effects on both astrocytes and oligodendrocytes that surround the nerve axons (glial cells). It also acts to alternate the selection of neurotransmitters in sensory neurons (from noradrenaline to acetylcholine). LIF is produced by skeletal muscle when under load or after injury and stimulates the proliferation of satellite cells while inhibiting their fusion into muscle tubes. Increased LIF production in damaged muscles or neurons can move along the axons to the nerve body (located for motor neurons in the dorsal root ganglion) leading to increased survival.
Actions of LIF in the hematopoietic system
Despite its initial identification as a stimulant and differentiator of myeloid leukemia, LIF has very little effect on hematopoietic cells. Although it has no stimulatory activity on its own, it has been shown to work with interleukin-3 (IL-3) in stimulating human stem cell proliferation.
Cancer and LIF
Various studies have shown that LIF promotes the expression of cachexia and weight loss in various cancers. Increased expression of LIF has been shown in many solid tumors including cancers of the breast, colon, and nasopharynx.
Important Note
The measurement of the Leukemia Inhibitory Factor (LIF) is only performed for research purposes in the context of clinical studies and experimental protocols.
