L8.3 Inflammatory signal in skeletal muscles

Question 1

Difference between chronic & acute inflammation

Answer 1

Chronic: Related to muscle atrophy/myopathy
Acute: Helps with muscle hypertrophy (after exercise)

Question 2

What is the response and timeframe following muscle injury?

Answer 2

• Destruction → repair → Remodelling
• Main timeframe for immune cell involvement following muscle injury is 0-14 days:
  
  • 0-2 days: neutrophils
  • ~3-7 days: Macrophages
  • ~9th day (peak): T-lymphocytes

Question 3

What is needed for complete muscle repair and adaptations?

Answer 3

Macrophages

Question 4

How is the response to stress different?

Answer 4

• Sepsis: TNF triggered first, followed by IL-6
• Exercise: Plasma IL-6 main, TNF hardly activated
  
  • Amount released depends on type, duration, intensity

Question 5

What are the different pathways which IL6, insulin/IGF1, TNF operates through?

Answer 5

• IL 6 through JAK/STAT
• Insulin & IGF1 through JAK/STAT
• TNF through JNK

Question 6

What is the JAK/STAT pathway?

Answer 6

• IL6 binds to gp130 Receptor
• → JAK phosphorylated
• → phosphorylates STAT (IL6 activated through STAT 3)
• → translocated to nuclei
• → SOCS3 (-ve FB)
• → inhibits JAK/STAT phosphorylation

Question 7

STAT3

Answer 7

• Ex → ↑STAT3 (Resistance)
  
  • Facilitates transcription of genes
• ↑STAT3 → ∴ ↑SOCS3
• STAT 5 also ↑ (but induced from aerobic exercise-induced release of GH)

Question 8

Factors regulating immune response: Exercise

Answer 8

• IL6 & STAT3 response is irrespective of training status; still needed for inflammatory response to occur to mediate muscle adaptations

Question 9

Factors regulating immune response: Aging

Answer 9

• ↑ROS with age → inflammation response altered
• WBC release: no age related difference
• BUT Macrophages: young>old
• IL6:
  
  • Basal: old>young
  • Post-ex:
    
    • Plasma: young>old
    • Muscular: Old>young
• SOCS3: Young>old → ∴allows ↑STAT3 for old

Question 10

Factors regulating immune response: Gender

Answer 10

• Different response, may be due to hormonal levels
• Post exercise RBC neutrophil response: female>male
  
  • Although females have elevated initial immune response, this is not reflected by infiltration of macrophages 24hrs post-exercise
• IL6 & STAT3: No diff.

Question 11

Factors regulating immune response: Medication

Answer 11

• Blunted protein synthesis post-ex from medications (acetaminoplen & Ibuprofen)
• -↓IL6 & IL10
• NSAIDs → blunted sat cells reponse & muscle regeneration
  
  • Blocks Pax7